Identification of a new p53 responsive element in the promoter region of anillin

Ma,Jiao; Liu,Xinying; Liu,Pengyi; Lu,Wenqing; Shen,Xinxin; Ma,Ruixiang; Zong,Hongliang

doi:10.3892/ijmm.2020.4527

Identification of a new p53 responsive element in the promoter region of anillin

Authors:
- Jiao Ma
- Xinying Liu
- Pengyi Liu
- Wenqing Lu
- Xinxin Shen
- Ruixiang Ma
- Hongliang Zong
View Affiliations

Affiliations: Department of Biochemistry and Molecular Cell Biology, Shanghai Jiaotong University Medical School, Shanghai 200025, P.R. China, Shanghai PerHum Therapeutics Co. Ltd., Shanghai 200052, P.R. China
Published online on: March 4, 2020 https://doi.org/10.3892/ijmm.2020.4527
Pages: 1563-1570

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The expression of anillin mRNA and protein is regulated in a cell cycle‑dependent manner. However, the mechanism underlying this process is unclear. Previous studies analyzing the sequence of the 5'‑untranslated region of anillin have unveiled several putative p53 binding sites. Therefore, the present study hypothesized that the anillin gene may be repressed by p53 and that the commonly observed mutation (or loss of function) of p53 may serve a role in this phenotype. Bioinformatic analysis of the anillin promoter region revealed potential p53 responsive elements. Of those identified, 2 were able to bind p53 protein, as determined via a chromatin immunoprecipitation assay. Although it was hypothesized that DNA damage and resultant p53 expression would repress anillin expression, the results revealed that anillin mRNA and protein expression levels were negatively regulated by DNA damage in the wild‑type p53 cells, but not in the isogenic p53 null cells. Furthermore, DNA sequences encompassing the p53 binding site downregulated luciferase transgenes in a p53 dependent manner. Taken together, these data indicated that anillin was negatively regulated by p53 and that anillin overexpression observed in cancer may be a p53‑mediated phenomenon. The data from the present study provided further evidence for the role of p53 in the biologically crucial process of cytokinesis.

View Figures

View References

1	Field CM and Alberts BM: Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. J Cell Biol. 131:165–178. 1995. View Article : Google Scholar : PubMed/NCBI
2	Kim H, Johnson JM, Lera RF, Brahma S and Burkard ME: Anillin phosphorylation controls timely membrane association and successful cytokinesis. PLoS Genet. 13:e10065112017. View Article : Google Scholar : PubMed/NCBI
3	Pollard TD and O’Shaughnessy B: Molecular mechanism of cytokinesis. Annu Rev Biochem. 88:661–689. 2019. View Article : Google Scholar : PubMed/NCBI
4	Zeng S, Yu X, Ma C, Song R, Zhang Z, Zi X, Chen X, Wang Y, Yu Y, Zhao J, et al: Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma. Sci Rep. 7:31512017. View Article : Google Scholar : PubMed/NCBI
5	Beaudet D, Akhshi T, Phillipp J, Law C and Piekny A: Active Ran regulates anillin function during cytokinesis. Mol Biol Cell. 28:3517–3531. 2017. View Article : Google Scholar : PubMed/NCBI
6	Zhang S, Nguyen LH, Zhou K, Tu HC, Sehgal A, Nassour I, Li L, Gopal P, Goodman J, Singal AG, et al: Knockdown of anillin actin binding protein blocks cytokinesis in hepatocytes and reduces liver tumor development in mice without affecting regeneration. Gastroenterology. 154:1421–1434. 2018. View Article : Google Scholar :
7	Erwig MS, Patzig J, Steyer AM, Dibaj P, Heilmann M, Heilmann I, Jung RB, Kusch K, Möbius W, Jahn O, et al: Anillin facilitates septin assembly to prevent pathological outfoldings of central nervous system myelin. Elife. 8:pii: e43888. 2019. View Article : Google Scholar : PubMed/NCBI
8	Yasuda T, Takaine M, Numata O and Nakano K: Anillin-related protein Mid1 regulates timely formation of the contractile ring in the fission yeast Schizosaccharomyces japonicus. Genes Cells. 21:594–607. 2016. View Article : Google Scholar : PubMed/NCBI
9	Gregory SL, Ebrahimi S, Milverton J, Jones WM, Bejsovec A and Saint R: Cell division requires a direct link between microtubule-bound RacGAP and anillin in the contractile ring. Curr Biol. 18:25–29. 2008. View Article : Google Scholar
10	Glotzer M: Cytokinesis in metazoa and fungi. Cold Spring Harb Perspect Biol. 9:pii: a022343. 2017. View Article : Google Scholar
11	Zhao WM and Fang G: Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial contractility of myosin during late cytokinesis. J Biol Chem. 280:33516–33524. 2005. View Article : Google Scholar : PubMed/NCBI
12	Perez AM and Thorner J: Septin-associated proteins Aim44 and Nis1 traffic between the bud neck and the nucleus in the yeast Saccharomyces cerevisiae. Cytoskeleton (Hoboken). 76:15–32. 2019. View Article : Google Scholar
13	Wang D, Chadha GK, Feygin A and Ivanov AI: F-actin binding protein, anillin, regulates integrity of intercellular junctions in human epithelial cells. Cell Mol Life Sci. 72:3185–3200. 2015. View Article : Google Scholar : PubMed/NCBI
14	Stauffer S, Zeng Y, Zhou J, Chen X, Chen Y and Dong J: CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity. Cell Signal. 39:74–83. 2017. View Article : Google Scholar : PubMed/NCBI
15	Hall PA, Todd CB, Hyland PL, McDade SS, Grabsch H, Dattani M, Hillan KJ and Russell SE: The septin-binding protein anillin is overexpressed in diverse human tumors. Clin Cancer Res. 11:6780–6786. 2005. View Article : Google Scholar : PubMed/NCBI
16	Magnusson K, Gremel G, Rydén L, Pontén V, Uhlén M, Dimberg A, Jirström K and Pontén F: ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer. BMC Cancer. 16:9042016. View Article : Google Scholar : PubMed/NCBI
17	Pandi NS, Manimuthu M, Harunipriya P, Murugesan M, Asha GV and Rajendran S: In silico analysis of expression pattern of a Wnt/β-catenin responsive gene ANLN in gastric cancer. Gene. 545:23–29. 2014. View Article : Google Scholar : PubMed/NCBI
18	Idichi T, Seki N, Kurahara H, Yonemori K, Osako Y, Arai T, Okato A, Kita Y, Arigami T, Mataki Y, et al: Regulation of actin-binding protein ANLN by antitumor miR-217 inhibits cancer cell aggressiveness in pancreatic ductal adenocarcinoma. Oncotarget. 8:53180–53193. 2017. View Article : Google Scholar : PubMed/NCBI
19	Lian YF, Huang YL, Wang JL, Deng MH, Xia TL, Zeng MS, Chen MS, Wang HB and Huang YH: Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma. Aging (Albany NY). 10:1884–1901. 2018. View Article : Google Scholar
20	Shimizu S, Seki N, Sugimoto T, Horiguchi S, Tanzawa H, Hanazawa T and Okamoto Y: Identification of molecular targets in head and neck squamous cell carcinomas based on genome-wide gene expression profiling. Oncol Rep. 18:1489–1497. 2007.PubMed/NCBI
21	Suzuki C, Daigo Y, Ishikawa N, Kato T, Hayama S, Ito T, Tsuchiya E and Nakamura Y: ANLN plays a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway. Cancer Res. 65:11314–11325. 2005. View Article : Google Scholar : PubMed/NCBI
22	Mirza A, Wu Q, Wang L, McClanahan T, Bishop WR, Gheyas F, Ding W, Hutchins B, Hockenberry T, Kirschmeier P, et al: Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression. Oncogene. 22:3645–3654. 2003. View Article : Google Scholar : PubMed/NCBI
23	Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM and Haussler D: The human genome browser at UCSC. Genome Res. 12:996–1006. 2002. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	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
26	Zhong B, Shingyoji M, Hanazono M, Nguyễn TTT, Morinaga T, Tada Y, Hiroshima K, Shimada H and Tagawa M: A p53-stabilizing agent, CP-31398, induces p21 expression with increased G2/M phase through the YY1 transcription factor in esophageal carcinoma defective of the p53 pathway. Am J Cancer Res. 9:79–93. 2019.PubMed/NCBI
27	Johmura Y and Nakanishi M: Multiple facets of p53 in senescence induction and maintenance. Cancer Sci. 107:1550–1555. 2016. View Article : Google Scholar : PubMed/NCBI
28	Luo Q, Guo H, Kuang P, Cui H, Deng H, Liu H, Lu Y, Wei Q, Chen L, Fang J, et al: Sodium fluoride arrests renal G2/M phase cell-cycle progression by activating ATM-Chk2-P53/Cdc25C signaling pathway in mice. Cell Physiol Biochem. 51:2421–2433. 2018. View Article : Google Scholar : PubMed/NCBI
29	Meitinger F, Anzola JV, Kaulich M, Richardson A, Stender JD, Benner C, Glass CK, Dowdy SF, Desai A, Shiau AK and Oegema K: 53BP1 and USP28 mediate p53 activation and G1 arrest after centrosome loss or extended mitotic duration. J Cell Biol. 214:155–166. 2016. View Article : Google Scholar : PubMed/NCBI
30	Zhang B, Shi X, Xu G, Kang W, Zhang W, Zhang S, Cao Y, Qian L, Zhan P, Yan H, et al: Elevated PRC1 in gastric carcinoma exerts oncogenic function and is targeted by piperlongumine in a p53-dependent manner. J Cell Mol Med. 21:1329–1341. 2017. View Article : Google Scholar : PubMed/NCBI
31	Tsuchihara K, Lapin V, Bakal C, Okada H, Brown L, Hirota-Tsuchihara M, Zaugg K, Ho A, Itie-Youten A, Harris-Brandts M, et al: Ckap2 regulates aneuploidy, cell cycling, and cell death in a p53-dependent manner. Cancer Res. 65:6685–6691. 2005. View Article : Google Scholar : PubMed/NCBI
32	Hsu FF, Lin TY, Chen JY and Shieh SY: p53-mediated transactivation of LIMK2b links actin dynamics to cell cycle checkpoint control. Oncogene. 29:2864–2876. 2010. View Article : Google Scholar : PubMed/NCBI
33	Patzig J, Erwig MS, Tenzer S, Kusch K, Dibaj P, Möbius W, Goebbels S, Schaeren-Wiemers N, Nave KA and Werner HB: Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction. Elife. 5:pii: e17119. 2016. View Article : Google Scholar : PubMed/NCBI
34	Kremer BE, Adang LA and Macara IG: Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell. 130:837–850. 2007. View Article : Google Scholar : PubMed/NCBI
35	Levine AJ, Puzio-Kuter AM, Chan CS and Hainaut P: The role of the p53 protein in stem-cell biology and epigenetic regulation. Cold Spring Harb Perspect Med. 6:pii: a026153. 2016. View Article : Google Scholar : PubMed/NCBI
36	Itahana Y, Zhang J, Göke J, Vardy LA, Han R, Iwamoto K, Cukuroglu E, Robson P, Pouladi MA, Colman A and Itahana K: Histone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells. Sci Rep. 6:281122016. View Article : Google Scholar : PubMed/NCBI
37	Chartier NT, Salazar Ospina DP, Benkemoun L, Mayer M, Grill SW, Maddox AS and Labbé JC: PAR-4/LKB1 mobilizes nonmuscle myosin through anillin to regulate C. elegans embryonic polarization and cytokinesis. Curr Biol. 21:259–269. 2011. View Article : Google Scholar : PubMed/NCBI
38	Sharif B, Fadero T and Maddox AS: Anillin localization suggests distinct mechanisms of division plane specification in mouse oogenic meiosis I and II. Gene Expr Patterns. 17:98–106. 2015. View Article : Google Scholar : PubMed/NCBI
39	Fox S, Southam P, Pantin F, Kennaway R, Robinson S, Castorina G, Sánchez-Corrales YE, Sablowski R, Chan J, Grieneisen V, et al: Spatiotemporal coordination of cell division and growth during organ morphogenesis. PLoS Biol. 16:e20059522018. View Article : Google Scholar : PubMed/NCBI
40	Pillitteri LJ, Guo X and Dong J: Asymmetric cell division in plants: Mechanisms of symmetry breaking and cell fate determination. Cell Mol Life Sci. 73:4213–4229. 2016. View Article : Google Scholar : PubMed/NCBI
41	Oegema K, Savoian MS, Mitchison TJ and Field CM: Functional analysis of a human homologue of the Drosophila actin binding protein anillin suggests a role in cytokinesis. J Cell Biol. 150:539–552. 2000. View Article : Google Scholar : PubMed/NCBI
42	Gieni RS and Hendzel MJ: Actin dynamics and functions in the interphase nucleus: Moving toward an understanding of nuclear polymeric actin. Biochem Cell Biol. 87:283–306. 2009. View Article : Google Scholar : PubMed/NCBI
43	Jones WM, Chao AT, Zavortink M, Saint R and Bejsovec A: Cytokinesis proteins Tum and Pav have a nuclear role in Wnt regulation. J Cell Sci. 123:2179–2189. 2010. View Article : Google Scholar : PubMed/NCBI
44	Guillemot L, Guerrera D, Spadaro D, Tapia R, Jond L and Citi S: MgcRacGAP interacts with cingulin and paracingulin to regulate Rac1 activation and development of the tight junction barrier during epithelial junction assembly. Mol Biol Cell. 25:1995–2005. 2014. View Article : Google Scholar : PubMed/NCBI