Identification and molecular analysis of <em>RNF31</em> Q622H germline polymorphism

Nakazawa,Seshiru; Mamiya,Ryo; Kawabata-Iwakawa,Reika; Oikawa,Daisuke; Kaira,Kyoichi; Tokunaga,Fuminori; Nobusawa,Sumihito; Sato,Yusuke; Sasaki,Atsushi; Yajima,Toshiki; Shirabe,Ken

doi:10.3892/ol.2022.13514

November-2022 Volume 24 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

November-2022 Volume 24 Issue 5

Full Size Image

Article Open Access

Identification and molecular analysis of RNF31 Q622H germline polymorphism

Authors:
- Seshiru Nakazawa
- Ryo Mamiya
- Reika Kawabata-Iwakawa
- Daisuke Oikawa
- Kyoichi Kaira
- Fuminori Tokunaga
- Sumihito Nobusawa
- Yusuke Sato
- Atsushi Sasaki
- Toshiki Yajima
- Ken Shirabe
View Affiliations / Copyright

Affiliations: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research, Maebashi, Gunma 371‑8511, Japan, Department of Medical Biochemistry, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Osaka 545‑8585, Japan, Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Saitama 350‑1298, Japan, Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Center for Research on Green Sustainable Chemistry, Tottori University, Tottori, Tottori 680‑8552, Japan, Department of Pathology, Saitama Medical University School of Medicine, Moroyama, Saitama 350‑0495, Japan, Department of Innovative Cancer Immunotherapy, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan

Copyright: © Nakazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 394
|
Published online on: September 21, 2022

https://doi.org/10.3892/ol.2022.13514
Expand metrics +

Abstract

The linear ubiquitin chain assembly complex (LUBAC), which is composed of RING finger protein 31 (RNF31), RANBP2‑type and C3HC4‑type zinc finger containing 1 and SHANK‑associated RH domain interactor subunits, is the only ubiquitin ligase to generate Met1‑linked linear ubiquitin chains. Linear ubiquitin chains regulate canonical NF‑κB activation and cell death. Single nucleotide polymorphisms in RNF31, such as Q584H and Q622L, are known to cause the activated B cell‑like subtype of diffuse large B cell lymphoma (ABC‑DLBCL) because of enhanced LUBAC‑mediated NF‑κB activation. The present study identified a novel Q622H polymorphism of RNF31 in two patients with lung cancer, one of whom had concurrent ABC‑DLBCL. Immunohistochemical analyses revealed that although the expression of RNF31 was elevated in both patients, only the ABC‑DLBCL specimen showed increased NF‑κB activation. Cancer panel analysis showed that the Q622H‑related ABC‑DLBCL did not harbor co‑mutations that were previously reported in Q584H‑/Q622L‑related ABC‑DLBCL. Furthermore, in contrast to Q584H and Q622L, Q622H showed no enhancement effects on LUBAC and NF‑κB activity in vitro compared with wild‑type RNF31. The present study's structural prediction suggested that the electrostatic interaction related to the Q622 residue may not have had an important role in LUBAC formation. In conclusion, the molecular mechanism and mutational background of RNF31 Q622H differed from that of RNF31 Q584H or Q622L. Furthermore, RNF31 Q622H appeared not to induce NF‑κB activation in lung cancer.

View Figures

View References

1	Yau R and Rape M: The increasing complexity of the ubiquitin code. Nat Cell Biol. 18:579–586. 2016. View Article : Google Scholar : PubMed/NCBI
2	Swatek KN and Komander D: Ubiquitin modifications. Cell Res. 26:399–422. 2016. View Article : Google Scholar : PubMed/NCBI
3	Grumati P and Dikic I: Ubiquitin signaling and autophagy. J Biol Chem. 293:5404–5413. 2018. View Article : Google Scholar : PubMed/NCBI
4	Popovic D, Vucic D and Dikic I: Ubiquitination in disease pathogenesis and treatment. Nat Med. 20:1242–1253. 2014. View Article : Google Scholar : PubMed/NCBI
5	Sasaki Y, Sano S, Nakahara M, Murata S, Kometani K, Aiba Y, Sakamoto S, Watanabe Y, Tanaka K, Kurosaki T and Iwai K: Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J. 32:2463–2476. 2013. View Article : Google Scholar : PubMed/NCBI
6	Teh CE, Lalaoui N, Jain R, Policheni AN, Heinlein M, Alvarez-Diaz S, Sheridan JM, Rieser E, Deuser S, Darding M, et al: Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis. Nat Commun. 7:133532016. View Article : Google Scholar : PubMed/NCBI
7	Redecke V, Chaturvedi V, Kuriakose J and Häcker H: SHARPIN controls the development of regulatory T cells. Immunology. 148:216–226. 2016. View Article : Google Scholar : PubMed/NCBI
8	Klein T, Fung SY, Renner F, Blank MA, Dufour A, Kang S, Bolger-Munro M, Scurll JM, Priatel JJ, Schweigler P, et al: The paracaspase MALT1 cleaves HOIL1 reducing linear ubiquitination by LUBAC to dampen lymphocyte NF-κB signalling. Nat Commun. 6:87772015. View Article : Google Scholar : PubMed/NCBI
9	Song Z, Wei W, Xiao W, Al-Saleem ED, Nejati R, Chen L, Yin J, Fabrizio J, Petrus MN, Waldmann TA and Yang Y: Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proc Natl Acad Sci USA. 117:28980–28991. 2020. View Article : Google Scholar : PubMed/NCBI
10	Yang Y, Schmitz R, Mitala J, Whiting A, Xiao W, Ceribelli M, Wright GW, Zhao H, Yang Y, Xu W, et al: Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms. Cancer Discov. 4:480–493. 2014. View Article : Google Scholar : PubMed/NCBI
11	Dubois SM, Alexia C, Wu Y, Leclair HM, Leveau C, Schol E, Fest T, Tarte K, Chen ZJ, Gavard J and Bidère N: A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells. Blood. 123:2199–2203. 2014. View Article : Google Scholar : PubMed/NCBI
12	Jo T, Nishikori M, Kogure Y, Arima H, Sasaki K, Sasaki Y, Nakagawa T, Iwai F, Momose S, Shiraishi A, et al: LUBAC accelerates B-cell lymphomagenesis by conferring resistance to genotoxic stress on B cells. Blood. 136:684–697. 2020. View Article : Google Scholar : PubMed/NCBI
13	Yokobori T, Bao P, Fukuchi M, Altan B, Ozawa D, Rokudai S, Bai T, Kumakura Y, Honjo H, Hara K, et al: Nuclear PROX1 is associated with hypoxia-inducible factor 1α expression and cancer progression in esophageal squamous cell carcinoma. Ann Surg Oncol. 22 (Suppl 3):S1566–S1573. 2015. View Article : Google Scholar : PubMed/NCBI
14	Sasaki A, Hirato J, Hirose T, Fukuoka K, Kanemura Y, Hashimoto N, Kodama Y, Ichimura K, Sakamoto H and Nishikawa R: Review of ependymomas: Assessment of consensus in pathological diagnosis and correlations with genetic profiles and outcome. Brain Tumor Pathol. 36:92–101. 2019. View Article : Google Scholar : PubMed/NCBI
15	Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, et al: COSMIC: The catalogue of somatic mutations in cancer. Nucleic Acids Res. 47(D1): D941–D947. 2019. View Article : Google Scholar : PubMed/NCBI
16	Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, Tanaka K, Nakano H and Iwai K: SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex. Nature. 471:633–636. 2011. View Article : Google Scholar : PubMed/NCBI
17	Tokunaga F, Sakata SI, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, et al: Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 11:123–132. 2009. View Article : Google Scholar : PubMed/NCBI
18	Fujita H, Tokunaga A, Shimizu S, Whiting AL, Aguilar-Alonso F, Takagi K, Walinda E, Sasaki Y, Shimokawa T, Mizushima T, et al: Cooperative domain formation by homologous motifs in HOIL-1L and SHARPIN plays A crucial role in LUBAC stabilization. Cell Rep. 23:1192–1204. 2018. View Article : Google Scholar : PubMed/NCBI
19	Yagi H, Ishimoto K, Hiromoto T, Fujita H, Mizushima T, Uekusa Y, Yagi-Utsumi M, Kurimoto E, Noda M, Uchiyama S, et al: A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex. EMBO Rep. 13:462–468. 2012. View Article : Google Scholar : PubMed/NCBI
20	Karin M: NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb Perspect Biol. 1:a0001412009. View Article : Google Scholar : PubMed/NCBI
21	Boisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M, Lidov HG, Hopkins G, Du L, Belkadi A, et al: Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 212:939–951. 2015. View Article : Google Scholar : PubMed/NCBI
22	Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, et al: Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 13:1178–1186. 2012. View Article : Google Scholar : PubMed/NCBI
23	Nilsson J, Schoser B, Laforet P, Kalev O, Lindberg C, Romero NB, Dávila López M, Akman HO, Wahbi K, Iglseder S, et al: Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann Neurol. 74:914–919. 2013. View Article : Google Scholar : PubMed/NCBI
24	Oda H, Beck DB, Kuehn HS, Sampaio Moura N, Hoffmann P, Ibarra M, Stoddard J, Tsai WL, Gutierrez-Cruz G, Gadina M, et al: Second case of HOIP deficiency expands clinical features and defines inflammatory transcriptome regulated by LUBAC. Front Immunol. 10:4792019. View Article : Google Scholar : PubMed/NCBI
25	Shimizu Y, Peltzer N, Sevko A, Lafont E, Sarr A, Draberova H and Walczak H: The linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis. Hepatology. 65:1963–1978. 2017. View Article : Google Scholar : PubMed/NCBI
26	Pomerantz JL: HOIP for targeting diffuse large B-cell lymphoma. Blood. 136:646–647. 2020. View Article : Google Scholar : PubMed/NCBI
27	Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, Heng JC, Dahlberg SE, Jänne PA, Verma S, et al: MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 34:721–730. 2016. View Article : Google Scholar : PubMed/NCBI
28	Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, Akimov M, Bufill JA, Lee C, Jentz D, et al: Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 5:850–859. 2015. View Article : Google Scholar : PubMed/NCBI