The Trim39 Ubiquitin Ligase Inhibits APC/CCdh1-mediated Degradation of the Bax Activator MOAP-1

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2012 Apr 25

PMID 22529100

Citations 36

Authors

Nai-Jia Huang

Liguo Zhang

Wanli Tang

Chen Chen

Chih-Sheng Yang

Sally Kornbluth

Affiliations

Soon will be listed here.

Abstract

Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. It was previously reported that modulator of apoptosis protein 1 (MOAP-1), an enhancer of Bax activation induced by DNA damage, is stabilized by Trim39, a protein of unknown function. In this paper, we show that MOAP-1 is a novel substrate of the anaphase-promoting complex (APC/C(Cdh1)) ubiquitin ligase. The influence of Trim39 on MOAP-1 levels stems from the ability of Trim39 (a RING domain E3 ligase) to directly inhibit APC/C(Cdh1)-mediated protein ubiquitylation. Accordingly, small interfering ribonucleic acid-mediated knockdown of Cdh1 stabilized MOAP-1, thereby enhancing etoposide-induced Bax activation and apoptosis. These data identify Trim39 as a novel APC/C regulator and provide an unexpected link between the APC/C and apoptotic regulation via MOAP-1.

Citing Articles

TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer.

Che X, Guan X, Ruan Y, Shen L, Shen Y, Liu H Front Med. 2024; 19(1):121-133.

PMID: 39643799 DOI: 10.1007/s11684-024-1103-5.

Regulation of Mitochondria-Derived Immune Activation by 'Antiviral' TRIM Proteins.

Oh S, Mandell M Viruses. 2024; 16(7).

PMID: 39066323 PMC: 11281404. DOI: 10.3390/v16071161.

The Diverse Evolutionary Histories of Domesticated Metaviral Capsid Genes in Mammals.

Henriques W, Young J, Nemudryi A, Nemudraia A, Wiedenheft B, Malik H Mol Biol Evol. 2024; 41(4).

PMID: 38507667 PMC: 11011659. DOI: 10.1093/molbev/msae061.

Multipronged regulation of autophagy and apoptosis: emerging role of TRIM proteins.

Ahsan N, Shariq M, Surolia A, Raj R, Khan M, Kumar P Cell Mol Biol Lett. 2024; 29(1):13.

PMID: 38225560 PMC: 10790450. DOI: 10.1186/s11658-023-00528-8.

A secreted form of chorismate mutase (Rv1885c) in Mycobacterium bovis BCG contributes to pathogenesis by inhibiting mitochondria-mediated apoptotic cell death of macrophages.

Lee M, Kim H, Seo H, Jung S, Kim B J Biomed Sci. 2023; 30(1):95.

PMID: 38110948 PMC: 10729386. DOI: 10.1186/s12929-023-00988-2.

References

Antonsson B, Montessuit S, Sanchez B, Martinou J . Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J Biol Chem. 2001; 276(15):11615-23. DOI: 10.1074/jbc.M010810200. View

Eskes R, Desagher S, Antonsson B, Martinou J . Bid induces the oligomerization and insertion of Bax into the outer mitochondrial membrane. Mol Cell Biol. 2000; 20(3):929-35. PMC: 85210. DOI: 10.1128/MCB.20.3.929-935.2000. View

Orimo A, Yamagishi T, Tominaga N, Yamauchi Y, Hishinuma T, Okada K . Molecular cloning of testis-abundant finger Protein/Ring finger protein 23 (RNF23), a novel RING-B box-coiled coil-B30.2 protein on the class I region of the human MHC. Biochem Biophys Res Commun. 2000; 276(1):45-51. DOI: 10.1006/bbrc.2000.3380. View

Colombo S, Palacios-Callender M, Frakich N, Leon J, Schmitt C, Boorn L . Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. Proc Natl Acad Sci U S A. 2010; 107(44):18868-73. PMC: 2973876. DOI: 10.1073/pnas.1012362107. View

Lee S, Fu N, Sukumaran S, Wan K, Wan Q, Yu V . TRIM39 is a MOAP-1-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. Exp Cell Res. 2008; 315(7):1313-25. DOI: 10.1016/j.yexcr.2008.11.021. View

Vos M, Dallol A, Eckfeld K, Allen N, Donninger H, Hesson L . The RASSF1A tumor suppressor activates Bax via MOAP-1. J Biol Chem. 2005; 281(8):4557-63. DOI: 10.1074/jbc.M512128200. View

Liu W, Li W, Fujita T, Yang Q, Wan Y . Proteolysis of CDH1 enhances susceptibility to UV radiation-induced apoptosis. Carcinogenesis. 2008; 29(2):263-72. DOI: 10.1093/carcin/bgm251. View

Antonsson B . Bax and other pro-apoptotic Bcl-2 family "killer-proteins" and their victim the mitochondrion. Cell Tissue Res. 2001; 306(3):347-61. DOI: 10.1007/s00441-001-0472-0. View

Deshaies R, Joazeiro C . RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009; 78:399-434. DOI: 10.1146/annurev.biochem.78.101807.093809. View

10.

Casaletto J, Nutt L, Wu Q, Moore J, Etkin L, Jackson P . Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase. J Cell Biol. 2005; 169(1):61-71. PMC: 2171901. DOI: 10.1083/jcb.200411056. View

11.

Almeida A, Bolanos J, Moreno S . Cdh1/Hct1-APC is essential for the survival of postmitotic neurons. J Neurosci. 2005; 25(36):8115-21. PMC: 6725543. DOI: 10.1523/JNEUROSCI.1143-05.2005. View

12.

Tan K, Fu N, Sukumaran S, Chan S, Kang J, Poon K . MAP-1 is a mitochondrial effector of Bax. Proc Natl Acad Sci U S A. 2005; 102(41):14623-8. PMC: 1239892. DOI: 10.1073/pnas.0503524102. View

13.

Horn S, Thomenius M, Johnson E, Freel C, Wu J, Coloff J . Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability. Mol Biol Cell. 2011; 22(8):1207-16. PMC: 3078078. DOI: 10.1091/mbc.E10-07-0567. View

14.

Sugimoto N, Kitabayashi I, Osano S, Tatsumi Y, Yugawa T, Narisawa-Saito M . Identification of novel human Cdt1-binding proteins by a proteomics approach: proteolytic regulation by APC/CCdh1. Mol Biol Cell. 2007; 19(3):1007-21. PMC: 2262995. DOI: 10.1091/mbc.e07-09-0859. View

15.

Aulia S, Tang B . Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer's disease pathology. Biochem Biophys Res Commun. 2005; 339(1):1-6. DOI: 10.1016/j.bbrc.2005.10.059. View

16.

Schuller M, Jenne D, Voltz R . The human PNMA family: novel neuronal proteins implicated in paraneoplastic neurological disease. J Neuroimmunol. 2005; 169(1-2):172-6. DOI: 10.1016/j.jneuroim.2005.08.019. View

17.

Tang W, Wu J, Chen C, Yang C, Guo J, Freel C . Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism. Mol Biol Cell. 2010; 21(15):2589-97. PMC: 2912346. DOI: 10.1091/mbc.E09-08-0708. View

18.

Harley M, Allan L, Sanderson H, Clarke P . Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 2010; 29(14):2407-20. PMC: 2910263. DOI: 10.1038/emboj.2010.112. View

19.

Tan K, Tan K, Chan S, Yee K, Bevort M, Ang K . MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J Biol Chem. 2000; 276(4):2802-7. DOI: 10.1074/jbc.M008955200. View

20.

Song M, Carracedo A, Salmena L, Song S, Egia A, Malumbres M . Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell. 2011; 144(2):187-99. PMC: 3249980. DOI: 10.1016/j.cell.2010.12.020. View