Skip to main content
NCBI home page
Protein & Cell logoLink to Protein & Cell
. 2010 Jul 29;1(7):656–663. doi: 10.1007/s13238-010-0083-1

RNF152, a novel lysosome localized E3 ligase with pro-apoptotic activities

Songling Zhang 1,2, Wei Wu 1, Yanfang Wu 1, Jiyan Zheng 1, Talin Suo 1, Hong Tang 1,✉, Jie Tang 1,✉
PMCID: PMC4875278  PMID: 21203937

Abstract

RING finger protein 152 (RNF152) is a novel RING finger protein and has not been well characterized. We report here that RNF152 is a canonical RING finger protein and has E3 ligase activity. It is polyubiqitinated partly through Lys-48-linked ubiquitin chains in vivo and this phenomenon is dependent on its RING finger domain and transmembrane domain. RNF152 is localized in lysosomes and co-localized with LAMP3, a lysosome marker. Moreover, over-expression of RNF152 in Hela cells induces apoptosis. These results suggest that RNF152 is a lysosome localized E3 ligase with pro-apoptotic activities. It is the first E3 ligase identified so far that is involved in lysosome-related apoptosis.

Keywords: RNF152, RING finger, ubiquitinate, apoptosis

Footnotes

These authors contributed equally to the work.

Contributor Information

Hong Tang, Email: tanghong@moon.ibp.ac.cn.

Jie Tang, Email: jtang@sun5.ibp.ac.cn.

References

  1. Autefage H., Albinet V., Garcia V., Berges H., Nicolau M.L., Therville N., Altié M.F., Caillaud C., Levade T., Andrieu-Abadie N. Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner. J Biol Chem. 2009;284:11507–11516. doi: 10.1074/jbc.M807151200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barlow P.N., Luisi B., Milner A., Elliott M., Everett R. Structure of the C3HC4 domain by 1H-nuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J Mol Biol. 1994;237:201–211. doi: 10.1006/jmbi.1994.1222. [DOI] [PubMed] [Google Scholar]
  3. Basu A., Haldar S. Signal-induced site specific phosphorylation targets Bcl2 to the proteasome pathway. Int J Oncol. 2002;21:597–601. [PubMed] [Google Scholar]
  4. Borden K.L., Boddy M.N., Lally J., O’Reilly N.J., Martin S., Howe K., Solomon E., Freemont P.S. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J. 1995;14:1532–1541. doi: 10.1002/j.1460-2075.1995.tb07139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boya P., Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene. 2008;27:6434–6451. doi: 10.1038/onc.2008.310. [DOI] [PubMed] [Google Scholar]
  6. Chwieralski C.E., Welte T., Bühling F. Cathepsin-regulated apoptosis. Apoptosis. 2006;11:143–149. doi: 10.1007/s10495-006-3486-y. [DOI] [PubMed] [Google Scholar]
  7. Deshaies R.J., Joazeiro C.A. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399–434. doi: 10.1146/annurev.biochem.78.101807.093809. [DOI] [PubMed] [Google Scholar]
  8. Guicciardi M.E., Leist M., Gores G.J. Lysosomes in cell death. Oncogene. 2004;23:2881–2890. doi: 10.1038/sj.onc.1207512. [DOI] [PubMed] [Google Scholar]
  9. Hershko A., Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479. doi: 10.1146/annurev.biochem.67.1.425. [DOI] [PubMed] [Google Scholar]
  10. Ikeda, K., Inoue, S., and Muramatsu, M. (2005). RING Finger-B Box-Coiled Coil (RBCC) proteins as ubiquitin ligase in the control of protein degradation and gene regulation. In, pp. 106–113.
  11. Lee D.H., Goldberg A.L. Proteasome inhibitors: valuable new tools for cell biologists. Trends Cell Biol. 1998;8:397–403. doi: 10.1016/S0962-8924(98)01346-4. [DOI] [PubMed] [Google Scholar]
  12. Ley R., Balmanno K., Hadfield K., Weston C., Cook S.J. Activation of the ERK1/2 signaling pathway promotes phosphorylation and proteasome-dependent degradation of the BH3-only protein, Bim. J Biol Chem. 2003;278:18811–18816. doi: 10.1074/jbc.M301010200. [DOI] [PubMed] [Google Scholar]
  13. Li W., Bengtson M.H., Ulbrich A., Matsuda A., Reddy V.A., Orth A., Chanda S.K., Batalov S., Joazeiro C.A., Ploegh H. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling. PLoS ONE. 2008;3:e1487. doi: 10.1371/journal.pone.0001487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Liston P., Fong W.G., Kelly N.L., Toji S., Miyazaki T., Conte D., Tamai K., Craig C.G., McBurney M.W., Korneluk R.G. Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001;3:128–133. doi: 10.1038/35055027. [DOI] [PubMed] [Google Scholar]
  15. Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S., Weissman A.M. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci U S A. 1999;96:11364–11369. doi: 10.1073/pnas.96.20.11364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Petroski M.D., Deshaies R.J. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6:9–20. doi: 10.1038/nrm1547. [DOI] [PubMed] [Google Scholar]
  17. Stoka V., Turk V., Turk B. Lysosomal cysteine cathepsins: signaling pathways in apoptosis. Biol Chem. 2007;388:555–560. doi: 10.1515/BC.2007.064. [DOI] [PubMed] [Google Scholar]
  18. Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., Altschul S.F., the Mammalian Gene Collection Program Team et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci U S A. 2002;99:16899–16903. doi: 10.1073/pnas.242603899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Takahashi R., Deveraux Q., Tamm I., Welsh K., Assa-Munt N., Salvesen G.S., Reed J.C. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem. 1998;273:7787–7790. doi: 10.1074/jbc.273.14.7787. [DOI] [PubMed] [Google Scholar]
  20. van der Reijden B.A., Erpelinck-Verschueren C.A., Löwenberg B., Jansen J.H. TRIADs: a new class of proteins with a novel cysteine-rich signature. Protein Sci. 1999;8:1557–1561. doi: 10.1110/ps.8.7.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weissman A.M. Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol. 2001;2:169–178. doi: 10.1038/35056563. [DOI] [PubMed] [Google Scholar]
  22. Yamamoto F., Yamamoto M. Scanning copy number and gene expression on the 18q21-qter chromosomal region by the systematic multiplex PCR and reverse transcription-PCR methods. Electrophoresis. 2007;28:1882–1895. doi: 10.1002/elps.200700093. [DOI] [PubMed] [Google Scholar]
  23. Yang Y., Fang S., Jensen J.P., Weissman A.M., Ashwell J.D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 2000;288:874–877. doi: 10.1126/science.288.5467.874. [DOI] [PubMed] [Google Scholar]
  24. Yang Y., Yu X. Regulation of apoptosis: the ubiquitous way. FASEB J. 2003;17:790–799. doi: 10.1096/fj.02-0654rev. [DOI] [PubMed] [Google Scholar]
  25. Zhang H.G., Wang J., Yang X., Hsu H.C., Mountz J.D. Regulation of apoptosis proteins in cancer cells by ubiquitin. Oncogene. 2004;23:2009–2015. doi: 10.1038/sj.onc.1207373. [DOI] [PubMed] [Google Scholar]
  26. Zheng N., Wang P., Jeffrey P.D., Pavletich N.P. Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Cell. 2000;102:533–539. doi: 10.1016/S0092-8674(00)00057-X. [DOI] [PubMed] [Google Scholar]

Articles from Protein & Cell are provided here courtesy of Oxford University Press

RESOURCES