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Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review)

  • Authors:
    • Luis Antonio Flores-López
    • Sergio Enríquez-Flores
    • Ignacio De La Mora-De La Mora
    • Itzhel García-Torres
    • Gabriel López-Velázquez
    • Rubí Viedma-Rodríguez
    • Alejandro Ávalos-Rodríguez
    • Alejandra Contreras-Ramos
    • Clara Ortega-Camarillo
  • View Affiliations / Copyright

    Affiliations: Biomolecules and Infant Health Laboratory, National Council of Humanities, Sciences and Technologies-National Institute of Pediatrics, Ministry of Health, Mexico City 04530, Mexico, Biomolecules and Infant Health Laboratory, National Institute of Pediatrics, Ministry of Health, Mexico City 04530, Mexico, Morphophysiology Unit, Faculty of Higher Studies, Iztacala, National Autonomous University of Mexico, Tlalnepantla 54090, Mexico, Department of Agricultural and Animal Production, Metropolitan Autonomous University-Xoch, Mexico City 04960, México, Molecular Biology Research Laboratory, Children's Hospital of Mexico Federico Gomez, Mexico City 06720, Mexico, Medical Research Unit in Biochemistry, Specialties Hospital, National Medical Center SXXI, Mexican Social Security Institute, Mexico City 06720, Mexico
    Copyright: © Flores-López et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 193
    |
    Published online on: August 27, 2024
       https://doi.org/10.3892/mmr.2024.13317
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Abstract

Pancreatic β‑cells are the only cells that synthesize insulin to regulate blood glucose levels. Various conditions can affect the mass of pancreatic β‑cells and decrease insulin levels. Diabetes mellitus is a disease characterized by insulin resistance and chronic hyperglycemia, mainly due to the loss of pancreatic β‑cells caused by an increase in the rate of apoptosis. Additionally, hyperglycemia has a toxic effect on β‑cells. Although the precise mechanism of glucotoxicity is not fully understood, several mechanisms have been proposed. The most prominent changes are increases in reactive oxygen species, the loss of mitochondrial membrane potential and the activation of the intrinsic pathway of apoptosis due to p53. The present review analyzed the location of p53 in the cytoplasm, mitochondria and nucleus in terms of post‑translational modifications, including phosphorylation, O‑GlcNAcylation and poly‑ADP‑ribosylation, under hyperglycemic conditions. These modifications protect p53 from degradation by the proteasome and, in turn, enable it to regulate the intrinsic pathway of apoptosis through the regulation of anti‑apoptotic and pro‑apoptotic elements. Degradation of p53 occurs in the proteasome and depends on its ubiquitination by Mdm2. Understanding the mechanisms that activate the death of pancreatic β‑cells will allow the proposal of treatment alternatives to prevent the decrease in pancreatic β‑cells.
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1 

Marchetti P, Bugliani M, De Tata V, Suleiman M and Marselli L: Pancreatic beta cell identity in humans and the role of type 2 diabetes. Front Cell Dev Biol. 5:552017. View Article : Google Scholar : PubMed/NCBI

2 

Wang P, Fiaschi-Taesch NM, Vasavada RC, Scott DK, García-Ocaña A and Stewart AF: Diabetes mellitus-advances and challenges in human β-cell proliferation. Nat Rev Endocrinol. 11:201–212. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Abdul-Ghani MA, Tripathy D and DeFronzo RA: Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care. 29:1130–1139. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, et al: IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 183:1091192022. View Article : Google Scholar : PubMed/NCBI

5 

Lin X, Xu Y, Pan X, Xu J, Ding Y, Sun X, Song X, Ren Y and Shan PF: Global, regional, and national burden and trend of diabetes in 195 countries and territories: An analysis from 1990 to 2025. Sci Rep. 10:147902020. View Article : Google Scholar : PubMed/NCBI

6 

International Diabetes Federation, . Diabetes Atlas. (10th Edition). https://fmdiabetes.org/atlas-idf-10o-edicion-2021/September 13–2023

7 

Harreiter J and Roden M: Diabetes mellitus: Definition, classification, diagnosis, screening and prevention (update 2023). Wien Klin Wochenschr. 135 (Suppl 1):S7–S17. 2023.(In German). View Article : Google Scholar : PubMed/NCBI

8 

Rojas J, Bermudez V, Palmar J, Martínez MS, Olivar LC, Nava M, Tomey D, Rojas M, Salazar J, Garicano C and Velasco M: Pancreatic beta cell death: Novel potential mechanisms in diabetes therapy. J Diabetes Res. 2018:96018012018. View Article : Google Scholar : PubMed/NCBI

9 

Barzalobre-Geronimo R, Contreras-Ramos A, Cervantes-Cruz AI, Cruz M, Suárez-Sánchez F, Goméz-Zamudio J, Diaz-Rosas G, Ávalos-Rodríguez A, Díaz-Flores M and Ortega-Camarillo C: Pancreatic β-cell apoptosis in normoglycemic rats is due to mitochondrial translocation of p53-induced by the consumption of sugar-sweetened beverages. Cell Biochem Biophys. 81:503–514. 2023. View Article : Google Scholar : PubMed/NCBI

10 

Barzalobre-Gerónimo R, Flores-López LA, Baiza-Gutman LA, Cruz M, García-Macedo R, Ávalos-Rodríguez A, Contreras-Ramos A, Díaz-Flores M and Ortega-Camarillo C: Erratum to: Hyperglycemia promotes p53-Mdm2 interaction but reduces p53 ubiquitination in RINm5F cells. Mol Cell Biochem. 406:3012015. View Article : Google Scholar : PubMed/NCBI

11 

Flores-López LA, Díaz-Flores M, García-Macedo R, Ávalos-Rodríguez A, Vergara-Onofre M, Cruz M, Contreras-Ramos A, Konigsberg M and Ortega-Camarillo C: High glucose induces mitochondrial p53 phosphorylation by p38 MAPK in pancreatic RINm5F cells. Mol Biol Rep. 40:4947–4958. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA and Butler PC: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 52:102–110. 2003. View Article : Google Scholar : PubMed/NCBI

13 

McFarland KF, Catalano EW, Day JF, Thorpe SR and Baynes JW: Nonenzymatic glucosylation of serum proteins in diabetes mellitus. Diabetes. 28:1011–1014. 1979. View Article : Google Scholar : PubMed/NCBI

14 

Tomita T: Apoptosis in pancreatic β-islet cells in type 2 diabetes. Bosn J Basic Med Sci. 16:162–179. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Chandra J, Zhivotovsky B, Zaitsev S, Juntti-Berggren L, Berggren PO and Orrenius S: Role of apoptosis in pancreatic beta-cell death in diabetes. Diabetes. 50 (Suppl 1):S44–S47. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Gottlieb TM and Oren M: p53 and apoptosis. Semin Cancer Biol. 8:359–368. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Ortega-Camarillo C, Guzmán-Grenfell AM, García-Macedo R, Rosales-Torres AM, Avalos-Rodríguez A, Durán-Reyes G, Medina-Navarro R, Cruz M, Díaz-Flores M and Kumate J: Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells. Mol Cell Biochem. 281:163–171. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Flores-López LA, Cruz-López M, García-Macedo R, Gómez-Olivares JL, Díaz-Flores M, Konigsberg-Fainstein M and Ortega-Camarillo C: Phosphorylation, O-N-acetylglucosaminylation and poly-ADP-ribosylation of P53 in RINm5F cells cultured in high glucose. Free Radic Biol Med. 53 (Suppl 2):S952012. View Article : Google Scholar

19 

DeLong MJ: Apoptosis: A modulator of cellular homeostasis and disease states. Ann N Y Acad Sci. 842:82–90. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Nicholson DW and Thornberry NA: Caspases: Killer proteases. Trends Biochem Sci. 22:299–306. 1997. View Article : Google Scholar : PubMed/NCBI

21 

Peter ME and Krammer PH: Mechanisms of CD95 (APO-1/Fas)-mediated apoptosis. Curr Opin Immunol. 10:545–551. 1998. View Article : Google Scholar : PubMed/NCBI

22 

Ichim G and Tait SWG: A fate worse than death: Apoptosis as an oncogenic process. Nat Rev Cancer. 16:539–548. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Johnson N, Khan A, Virji S, Ward JM and Crompton M: Import and processing of heart mitochondrial cyclophilin D. Eur J Biochem. 263:353–359. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Crompton M: Mitochondrial intermembrane junctional complexes and their role in cell death. J Physiol. 529:11–21. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Andreeva L, Heads R and Green CJ: Cyclophilins and their possible role in the stress response. Int J Exp Pathol. 80:305–315. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Marchenko ND, Zaika A and Moll UM: Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem. 275:16202–16212. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Lemasters JJ, Qian T, He L, Kim JS, Elmore SP, Cascio WE and Brenner DA: Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxid Redox Signal. 4:769–781. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, et al: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 397:441–446. 1999. View Article : Google Scholar : PubMed/NCBI

30 

Singh R, Letai A and Sarosiek K: Regulation of apoptosis in health and disease: The balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol. 20:175–193. 2019. View Article : Google Scholar : PubMed/NCBI

31 

Tsujimoto Y and Shimizu S: VDAC regulation by the Bcl-2 family of proteins. Cell Death Differ. 7:1174–1181. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C and Kroemer G: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 13:1423–1433. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Roche E: Diabetes tipo 2: Gluco-lipo-toxicidad y disfunción de la célula β pancreática. Ars Pharm. 44:313–332. 2003.

34 

Chen SS, Jiang T, Wang Y, Gu LZ, Wu HW, Tan L and Guo J: Activation of double-stranded RNA-dependent protein kinase inhibits proliferation of pancreatic β-cells. Biochem Biophys Res Commun. 443:814–820. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Yuan H, Zhang X, Huang X, Lu Y, Tang W, Man Y, Wang S, Xi J and Li J: NADPH oxidase 2-derived reactive oxygen species mediate FFAs-induced dysfunction and apoptosis of β-cells via JNK, p38 MAPK and p53 pathways. PLoS One. 5:e157262010. View Article : Google Scholar : PubMed/NCBI

36 

Lu H, Hao L, Li S, Lin S, Lv L, Chen Y, Cui H, Zi T, Chu X, Na L and Sun C: Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway. Diabetologia. 59:1247–1257. 2016. View Article : Google Scholar : PubMed/NCBI

37 

Mayo LD and Donner DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA. 98:11598–11603. 2001. View Article : Google Scholar : PubMed/NCBI

38 

Lytrivi M, Castell AL, Poitout V and Cnop M: Recent insights into mechanisms of β-Cell Lipo- and glucolipotoxicity in type 2 diabetes. J Mol Biol. 432:1514–1534. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Cunha DA, Igoillo-Esteve M, Gurzov EN, Germano CM, Naamane N, Marhfour I, Fukaya M, Vanderwinden JM, Gysemans C, Mathieu C, et al: Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis. Diabetes. 61:2763–2775. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Saltevo J, Vanhala M, Kautiainen H, Kumpusalo E and Laakso M: Association of C-reactive protein, interleukin-1 receptor antagonist and adiponectin with the metabolic syndrome. Mediators Inflamm. 2007:935732007. View Article : Google Scholar : PubMed/NCBI

41 

Hotamisligil GS: Inflammation and metabolic disorders. Nature. 444:860–867. 2006. View Article : Google Scholar : PubMed/NCBI

42 

Tilg H and Moschen AR: Inflammatory mechanisms in the regulation of insulin resistance. Mol Med. 14:222–231. 2008. View Article : Google Scholar : PubMed/NCBI

43 

Zhao YF and Chen C: Regulation of pancreatic beta-cell function by adipocytes. Sheng Li Xue Bao. 59:247–252. 2007.PubMed/NCBI

44 

Donath MY, Schumann DM, Faulenbach M, Ellingsgaard H, Perren A and Ehses JA: Islet inflammation in type 2 diabetes: From metabolic stress to therapy. Diabetes Care. 31 (Suppl 2):S161–S164. 2008. View Article : Google Scholar : PubMed/NCBI

45 

Eldor R, Yeffet A, Baum K, Doviner V, Amar D, Ben-Neriah Y, Christofori G, Peled A, Carel JC, Boitard C, et al: Conditional and specific NF-kappaB blockade protects pancreatic beta cells from diabetogenic agents. Proc Natl Acad Sci USA. 103:5072–5077. 2006. View Article : Google Scholar : PubMed/NCBI

46 

Nolan CJ, Madiraju MSR, Delghingaro-Augusto V, Peyot ML and Prentki M: Fatty acid signaling in the beta-cell and insulin secretion. Diabetes. 55 (Suppl 2):S16–S23. 2006. View Article : Google Scholar : PubMed/NCBI

47 

Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K and Tobe K: Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 116:1784–1792. 2006. View Article : Google Scholar : PubMed/NCBI

48 

Bensellam M, Laybutt DR and Jonas JC: The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions. Mol Cell Endocrinol. 364:1–27. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Brownlee M: The pathobiology of diabetic complications: A unifying mechanism. Diabetes. 54:1615–1625. 2005. View Article : Google Scholar : PubMed/NCBI

50 

Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C and Brownlee M: Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest. 112:1049–1057. 2003. View Article : Google Scholar : PubMed/NCBI

51 

Grankvist K, Marklund SL and Täljedal IB: CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J. 199:393–398. 1981. View Article : Google Scholar : PubMed/NCBI

52 

Gottlieb RA: Mitochondria: Execution central. FEBS Lett. 482:6–12. 2000. View Article : Google Scholar : PubMed/NCBI

53 

Schellenberg B, Wang P, Keeble JA, Rodriguez-Enriquez R, Walker S, Owens TW, Foster F, Tanianis-Hughes J, Brennan K, Streuli CH and Gilmore AP: Bax exists in a dynamic equilibrium between the cytosol and mitochondria to control apoptotic priming. Mol Cell. 49:959–971. 2013. View Article : Google Scholar : PubMed/NCBI

54 

Adams JM and Cory S: The Bcl-2 protein family: Arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI

55 

Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, Yang L, Lu B, Feng Z, Liu S and Wang F: Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase. Endocrinology. 148:81–91. 2007. View Article : Google Scholar : PubMed/NCBI

56 

Lawrence M, Shao C, Duan L, McGlynn K and Cobb MH: The protein kinases ERK1/2 and their roles in pancreatic beta cells. Acta Physiol (Oxf). 192:11–17. 2008. View Article : Google Scholar : PubMed/NCBI

57 

Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Segawa K, Ikeda Y and Kizaki M: Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: Implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species. Cancer Res. 64:1071–1078. 2004. View Article : Google Scholar : PubMed/NCBI

58 

Shen Y and White E: p53-dependent apoptosis pathways. Adv Cancer Res. 82:55–84. 2001. View Article : Google Scholar : PubMed/NCBI

59 

Green DR and Kroemer G: Cytoplasmic functions of the tumor suppressor p53. Nature. 458:1127–1130. 2009. View Article : Google Scholar : PubMed/NCBI

60 

Riley T, Sontag E, Chen P and Levine A: Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol. 9:402–412. 2008. View Article : Google Scholar : PubMed/NCBI

61 

Jenkins LM, Durell SR, Mazur SJ and Appella E: p53 N-terminal phosphorylation: A defining layer of complex regulation. Carcinogenesis. 33:1441–1449. 2012. View Article : Google Scholar : PubMed/NCBI

62 

el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW and Vogelstein B: Definition of a consensus binding site for p53. Nat Genet. 1:45–49. 1992. View Article : Google Scholar : PubMed/NCBI

63 

Ahn J and Prives C: The C-terminus of p53: The more you learn the less you know. Nat Struct Biol. 8:730–732. 2001. View Article : Google Scholar : PubMed/NCBI

64 

Aubrey BJ, Kelly GL, Janic A, Herold MJ and Strasser A: How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 25:104–113. 2018. View Article : Google Scholar : PubMed/NCBI

65 

Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP and Wang X: Prevention of apoptosis by Bcl-2: Release of cytochrome c from mitochondria blocked. Science. 275:1129–1132. 1997. View Article : Google Scholar : PubMed/NCBI

66 

Müller M, Wilder S, Bannasch D, Israeli D, Lehlbach K, Li-Weber M, Friedman SL, Galle PR, Stremmel W, Oren M and Krammer PH: p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J Exp Med. 188:2033–2045. 1998. View Article : Google Scholar : PubMed/NCBI

67 

Caelles C, Helmberg A and Karin M: p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature. 370:220–223. 1994. View Article : Google Scholar : PubMed/NCBI

68 

Sansome C, Zaika A, Marchenko ND and Moll UM: Hypoxia death stimulus induces translocation of p53 protein to mitochondria. Detection by immunofluorescence on whole cells. FEBS Lett. 488:110–115. 2001. View Article : Google Scholar : PubMed/NCBI

69 

Schuler M, Bossy-Wetzel E, Goldstein JC, Fitzgerald P and Green DR: p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J Biol Chem. 275:7337–7342. 2000. View Article : Google Scholar : PubMed/NCBI

70 

Donahue RJ, Razmara M, Hoek JB and Knudsen TB: Direct influence of the p53 tumor suppressor on mitochondrial biogenesis and function. FASEB J. 15:635–644. 2001. View Article : Google Scholar : PubMed/NCBI

71 

Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P and Moll UM: p53 has a direct apoptogenic role at the mitochondria. Mol Cell. 11:577–590. 2003. View Article : Google Scholar : PubMed/NCBI

72 

Wei H, Wang H, Wang G, Qu L, Jiang L, Dai S, Chen X, Zhang Y, Chen Z, Li Y, et al: Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity. Nat Commun. 14:43002023. View Article : Google Scholar : PubMed/NCBI

73 

Hinault C, Kawamori D, Liew CW, Maier B, Hu J, Keller SR, Mirmira RG, Scrable H and Kulkarni RN: Δ40 Isoform of p53 controls β-cell proliferation and glucose homeostasis in mice. Diabetes. 60:1210–1222. 2011. View Article : Google Scholar : PubMed/NCBI

74 

Kon N, Zhong J, Qiang L, Accili D and Gu W: Inactivation of arf-bp1 induces p53 activation and diabetic phenotypes in mice. J Biol Chem. 287:5102–5111. 2012. View Article : Google Scholar : PubMed/NCBI

75 

Uhlemeyer C, Müller N, Rieck M, Kuboth J, Schlegel C, Grieß K, Dorweiler TF, Heiduschka S, Eckel J, Roden M, et al: Selective ablation of P53 in pancreatic beta cells fails to ameliorate glucose metabolism in genetic, dietary and pharmacological models of diabetes mellitus. Mol Metab. 67:1016502023. View Article : Google Scholar : PubMed/NCBI

76 

Douc-Rasy S and Bénard J: A new view on p53 protein cytoplasmic sequestration. Bull Cancer. 90:380–382. 2003.(In French). PubMed/NCBI

77 

Giaccia AJ and Kastan MB: The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev. 12:2973–2983. 1998. View Article : Google Scholar : PubMed/NCBI

78 

Harris SL and Levine AJ: The p53 pathway: Positive and negative feedback loops. Oncogene. 24:2899–2908. 2005. View Article : Google Scholar : PubMed/NCBI

79 

Gonzalez-Rellan MJ, Fondevila MF, Fernandez U, Rodríguez A, Varela-Rey M, Veyrat-Durebex C, Seoane S, Bernardo G, Lopitz-Otsoa F, Fernández-Ramos D, et al: O-GlcNAcylated p53 in the liver modulates hepatic glucose production. Nat Commun. 12:50682021. View Article : Google Scholar : PubMed/NCBI

80 

Labuschagne CF, Zani F and Vousden KH: Control of metabolism by p53-cancer and beyond. Biochim Biophys Acta Rev Cancer. 1870:32–42. 2018. View Article : Google Scholar : PubMed/NCBI

81 

Yang WH, Kim JE, Nam HW, Ju JW, Kim HS, Kim YS and Cho JW: Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability. Nat Cell Biol. 8:1074–1083. 2006. View Article : Google Scholar : PubMed/NCBI

82 

Wen J and Wang D: Deciphering the PTM codes of the tumor suppressor p53. J Mol Cell Biol. 13:774–785. 2022. View Article : Google Scholar : PubMed/NCBI

83 

Liu Y, Tavana O and Gu W: p53 modifications: Exquisite decorations of the powerful guardian. J Mol Cell Biol. 11:564–577. 2019. View Article : Google Scholar : PubMed/NCBI

84 

Lavin MF and Gueven N: The complexity of p53 stabilization and activation. Cell Death Differ. 13:941–950. 2006. View Article : Google Scholar : PubMed/NCBI

85 

Thompson T, Tovar C, Yang H, Carvajal D, Vu BT, Xu Q, Wahl GM, Heimbrook DC and Vassilev LT: Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J Biol Chem. 279:53015–53022. 2004. View Article : Google Scholar : PubMed/NCBI

86 

Steegenga WT, van der Eb AJ and Jochemsen AG: How phosphorylation regulates the activity of p53. J Mol Biol. 263:103–113. 1996. View Article : Google Scholar : PubMed/NCBI

87 

Hoogervorst EM, Bruins W, Zwart E, van Oostrom CTM, van den Aardweg GJ, Beems RB, van den Berg J, Jacks T, van Steeg H and de Vries A: Lack of p53 Ser389 phosphorylation predisposes mice to develop 2-acetylaminofluorene-induced bladder tumors but not ionizing radiation-induced lymphomas. Cancer Res. 65:3610–3616. 2005. View Article : Google Scholar : PubMed/NCBI

88 

Park BS, Song YS, Yee SB, Lee BG, Seo SY, Park YC, Kim JM, Kim HM and Yoo YH: Phospho-ser 15-p53 translocates into mitochondria and interacts with Bcl-2 and Bcl-xL in eugenol-induced apoptosis. Apoptosis. 10:193–200. 2005. View Article : Google Scholar : PubMed/NCBI

89 

Fiordaliso F, Leri A, Cesselli D, Limana F, Safai B, Nadal-Ginard B, Anversa P and Kajstura J: Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death. Diabetes. 50:2363–2375. 2001. View Article : Google Scholar : PubMed/NCBI

90 

Malhotra A, Vashistha H, Yadav VS, Dube MG, Kalra SP, Abdellatif M and Meggs LG: Inhibition of p66ShcA redox activity in cardiac muscle cells attenuates hyperglycemia-induced oxidative stress and apoptosis. Am J Physiol Heart Circ Physiol. 296:H380–H388. 2009. View Article : Google Scholar : PubMed/NCBI

91 

Sumara G, Formentini I, Collins S, Sumara I, Windak R, Bodenmiller B, Ramracheya R, Caille D, Jiang H, Platt KA, et al: Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. Cell. 136:235–248. 2009. View Article : Google Scholar : PubMed/NCBI

92 

Evans JL, Goldfine ID, Maddux BA and Grodsky GM: Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocr Rev. 23:599–622. 2002. View Article : Google Scholar : PubMed/NCBI

93 

Chen K, Albano A, Ho A and Keaney JF Jr: Activation of p53 by oxidative stress involves platelet-derived growth factor-beta receptor-mediated ataxia telangiectasia mutated (ATM) kinase activation. J Biol Chem. 278:39527–39533. 2003. View Article : Google Scholar : PubMed/NCBI

94 

Thornton TM and Rincon M: Non-classical p38 map kinase functions: Cell cycle checkpoints and survival. Int J Biol Sci. 5:44–51. 2009. View Article : Google Scholar : PubMed/NCBI

95 

Nakagami H, Morishita R, Yamamoto K, Yoshimura SI, Taniyama Y, Aoki M, Matsubara H, Kim S, Kaneda Y and Ogihara T: Phosphorylation of p38 mitogen-activated protein kinase downstream of bax-caspase-3 pathway leads to cell death induced by high D-glucose in human endothelial cells. Diabetes. 50:1472–1481. 2001. View Article : Google Scholar : PubMed/NCBI

96 

She QB, Chen N and Dong Z: ERKs and p38 kinase phosphorylate p53 protein at serine 15 in response to UV radiation. J Biol Chem. 275:20444–20449. 2000. View Article : Google Scholar : PubMed/NCBI

97 

Fu X, Wan S, Lyu YL, Liu LF and Qi H: Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation. PLoS One. 3:e20092008. View Article : Google Scholar : PubMed/NCBI

98 

Barzilai A, Rotman G and Shiloh Y: ATM deficiency and oxidative stress: A new dimension of defective response to DNA damage. DNA Repair (Amst). 1:3–25. 2002. View Article : Google Scholar : PubMed/NCBI

99 

Reliene R, Fischer E and Schiestl RH: Effect of N-acetyl cysteine on oxidative DNA damage and the frequency of DNA deletions in atm-deficient mice. Cancer Res. 64:5148–5153. 2004. View Article : Google Scholar : PubMed/NCBI

100 

Uhlemeyer C, Müller N, Grieß K, Wessel C, Schlegel C, Kuboth J and Belgardt BF: ATM and P53 differentially regulate pancreatic beta cell survival in Ins1E cells. PLoS One. 15:e02376692020. View Article : Google Scholar : PubMed/NCBI

101 

Borges HL, Linden R and Wang JYJ: DNA damage-induced cell death: Lessons from the central nervous system. Cell Res. 18:17–26. 2008. View Article : Google Scholar : PubMed/NCBI

102 

Halaby MJ, Hibma JC, He J and Yang DQ: ATM protein kinase mediates full activation of Akt and regulates glucose transporter 4 translocation by insulin in muscle cells. Cell Signal. 20:1555–1563. 2008. View Article : Google Scholar : PubMed/NCBI

103 

Xu Y: Regulation of p53 responses by post-translational modifications. Cell Death Differ. 10:400–403. 2003. View Article : Google Scholar : PubMed/NCBI

104 

Hart GW, Slawson C, Ramirez-Correa G and Lagerlof O: Cross talk between O-GlcNAcylation and phosphorylation: Roles in signaling, transcription, and chronic disease. Annu Rev Biochem. 80:825–858. 2011. View Article : Google Scholar : PubMed/NCBI

105 

Jahangir Z, Ahmad W and Shabbiri K: Alternate phosphorylation/O-GlcNAc modification on human insulin IRSs: A road towards impaired insulin signaling in Alzheimer and diabetes. Adv Bioinformatics. 2014:3247532014. View Article : Google Scholar : PubMed/NCBI

106 

Bond MR and Hanover JA: O-GlcNAc cycling: A link between metabolism and chronic disease. Annu Rev Nutr. 33:205–229. 2013. View Article : Google Scholar : PubMed/NCBI

107 

Akimoto Y, Hart GW, Wells L, Vosseller K, Yamamoto K, Munetomo E, Ohara-Imaizumi M, Nishiwaki C, Nagamatsu S, Hirano H and Kawakami H: Elevation of the post-translational modification of proteins by O-linked N-acetylglucosamine leads to deterioration of the glucose-stimulated insulin secretion in the pancreas of diabetic Goto-Kakizaki rats. Glycobiology. 17:127–140. 2007. View Article : Google Scholar : PubMed/NCBI

108 

Schraufstatter IU, Hyslop PA, Hinshaw DB, Spragg RG, Sklar LA and Cochrane CG: Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase. Proc Natl Acad Sci USA. 83:4908–4912. 1986. View Article : Google Scholar : PubMed/NCBI

109 

D'Amours D, Desnoyers S, D'Silva I and Poirier GG: Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 342:249–268. 1999. View Article : Google Scholar : PubMed/NCBI

110 

Oliver FJ, Menissier-de Murcia J and de Murcia G: Poly(ADP-ribose) polymerase in the cellular response to DNA damage, apoptosis, and disease. Am J Hum Genet. 64:1282–1288. 1999. View Article : Google Scholar : PubMed/NCBI

111 

Elkholi R and Chipuk JE: How do I kill thee? Let me count the ways: p53 regulates PARP-1 dependent necrosis. Bioessays. 36:46–51. 2014. View Article : Google Scholar : PubMed/NCBI

112 

Ba X and Garg NJ: Signaling mechanism of poly(ADP-ribose) polymerase-1 (PARP-1) in inflammatory diseases. Am J Pathol. 178:946–955. 2011. View Article : Google Scholar : PubMed/NCBI

113 

Chaitanya GV, Steven AJ and Babu PP: PARP-1 cleavage fragments: Signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 8:312010. View Article : Google Scholar : PubMed/NCBI

114 

Li M, Brooks CL, Wu-Baer F, Chen D, Baer R and Gu W: Mono- versus polyubiquitination: Differential control of p53 fate by Mdm2. Science. 302:1972–1975. 2003. View Article : Google Scholar : PubMed/NCBI

115 

Feng J, Tamaskovic R, Yang Z, Brazil DP, Merlo A, Hess D and Hemmings BA: Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation. J Biol Chem. 279:35510–35517. 2004. View Article : Google Scholar : PubMed/NCBI

116 

Ogawara Y, Kishishita S, Obata T, Isazawa Y, Suzuki T, Tanaka K, Masuyama N and Gotoh Y: Akt enhances Mdm2-mediated ubiquitination and degradation of p53. J Biol Chem. 277:21843–21850. 2002. View Article : Google Scholar : PubMed/NCBI

117 

Fang S, Jensen JP, Ludwig RL, Vousden KH and Weissman AM: Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem. 275:8945–8951. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Flores-López LA, Enríquez-Flores S, De La Mora-De La Mora I, García-Torres I, López-Velázquez G, Viedma-Rodríguez R, Ávalos-Rodríguez A, Contreras-Ramos A and Ortega-Camarillo C: Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review). Mol Med Rep 30: 193, 2024.
APA
Flores-López, L.A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R. ... Ortega-Camarillo, C. (2024). Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review). Molecular Medicine Reports, 30, 193. https://doi.org/10.3892/mmr.2024.13317
MLA
Flores-López, L. A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R., Ávalos-Rodríguez, A., Contreras-Ramos, A., Ortega-Camarillo, C."Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review)". Molecular Medicine Reports 30.5 (2024): 193.
Chicago
Flores-López, L. A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R., Ávalos-Rodríguez, A., Contreras-Ramos, A., Ortega-Camarillo, C."Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review)". Molecular Medicine Reports 30, no. 5 (2024): 193. https://doi.org/10.3892/mmr.2024.13317
Copy and paste a formatted citation
x
Spandidos Publications style
Flores-López LA, Enríquez-Flores S, De La Mora-De La Mora I, García-Torres I, López-Velázquez G, Viedma-Rodríguez R, Ávalos-Rodríguez A, Contreras-Ramos A and Ortega-Camarillo C: Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review). Mol Med Rep 30: 193, 2024.
APA
Flores-López, L.A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R. ... Ortega-Camarillo, C. (2024). Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review). Molecular Medicine Reports, 30, 193. https://doi.org/10.3892/mmr.2024.13317
MLA
Flores-López, L. A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R., Ávalos-Rodríguez, A., Contreras-Ramos, A., Ortega-Camarillo, C."Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review)". Molecular Medicine Reports 30.5 (2024): 193.
Chicago
Flores-López, L. A., Enríquez-Flores, S., De La Mora-De La Mora, I., García-Torres, I., López-Velázquez, G., Viedma-Rodríguez, R., Ávalos-Rodríguez, A., Contreras-Ramos, A., Ortega-Camarillo, C."Pancreatic β‑cell apoptosis in type 2 diabetes is related to post‑translational modifications of p53 (Review)". Molecular Medicine Reports 30, no. 5 (2024): 193. https://doi.org/10.3892/mmr.2024.13317
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