CUL5 explained

Cullin-5 is a protein that in humans is encoded by the CUL5 gene.^{[1] [2] [3]}

Discovery

The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor.^[4] Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5.

Tissue distribution

Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules.^[5]

Function

Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation.^[6]

One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis.^[7]

Interactions

CUL5 has been shown to interact with RBX1.^{[8] [9]}

Further reading

• Hillier LD, Lennon G, Becker M . Generation and analysis of 280,000 human expressed sequence tags . Genome Res. . 6 . 9 . 807–28 . 1997 . 8889549 . 10.1101/gr.6.9.807 . etal. free .
• Stankovic T, Byrd PJ, Cooper PR . Construction of a transcription map around the gene for ataxia telangiectasia: identification of at least four novel genes . Genomics . 40 . 2 . 267–76 . 1997 . 9119394 . 10.1006/geno.1996.4595 . etal.
• North WG, Fay MJ, Longo KA, Du J . Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide . Cancer Res. . 58 . 9 . 1866–71 . 1998 . 9581826 .
• Burnatowska-Hledin M, Lazdins IB, Listenberger L . VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule . Am. J. Physiol. . 276 . 2 Pt 2 . F199–209 . 1999 . 10.1152/ajprenal.1999.276.2.F199 . 9950950 . etal.
• Wada H, Yeh ET, Kamitani T . Identification of NEDD8-conjugation site in human cullin-2 . Biochem. Biophys. Res. Commun. . 257 . 1 . 100–5 . 1999 . 10092517 . 10.1006/bbrc.1999.0339 .
• Ohta T, Michel JJ, Schottelius AJ, Xiong Y . ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity . Mol. Cell . 3 . 4 . 535–41 . 1999 . 10230407 . 10.1016/S1097-2765(00)80482-7 . 19371828 . free .
• Hori T, Osaka F, Chiba T . Covalent modification of all members of human cullin family proteins by NEDD8 . Oncogene . 18 . 48 . 6829–34 . 2000 . 10597293 . 10.1038/sj.onc.1203093 . etal. free .
• Burnatowska-Hledin M, Zhao P, Capps B . VACM-1, a cullin gene family member, regulates cellular signaling . Am. J. Physiol., Cell Physiol. . 279 . 1 . C266–73 . 2000 . 10898738 . 10.1152/ajpcell.2000.279.1.C266. 19845050 . etal.
• Kamura T, Burian D, Yan Q . Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase . J. Biol. Chem. . 276 . 32 . 29748–53 . 2001 . 11384984 . 10.1074/jbc.M103093200 . etal. free.
• Burnatowska-Hledin M, Zeneberg A, Roulo A . Expression of VACM-1 protein in cultured rat adrenal endothelial cells is linked to the cell cycle . Endothelium . 8 . 1 . 49–63 . 2001 . 11409851 . 10.3109/10623320109063157. etal.
• Harada JN, Shevchenko A, Shevchenko A . Analysis of the Adenovirus E1B-55K-Anchored Proteome Reveals Its Link to Ubiquitination Machinery . J. Virol. . 76 . 18 . 9194–206 . 2002 . 12186903 . 10.1128/JVI.76.18.9194-9206.2002 . 136464 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Liu J, Furukawa M, Matsumoto T, Xiong Y . NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases . Mol. Cell . 10 . 6 . 1511–8 . 2003 . 12504025 . 10.1016/S1097-2765(02)00783-9 . 28959307 . free .
• Van Dort C, Zhao P, Parmelee K . VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways . Am. J. Physiol., Cell Physiol. . 285 . 6 . C1386–96 . 2004 . 12917106 . 10.1152/ajpcell.00338.2002 . etal.
• Yu X, Yu Y, Liu B . Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex . Science . 302 . 5647 . 1056–60 . 2003 . 14564014 . 10.1126/science.1089591 . 2003Sci...302.1056Y . 29676466 . etal.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Burnatowska-Hledin MA, Kossoris JB, Van Dort CJ . T47D breast cancer cell growth is inhibited by expression of VACM-1, a cul-5 gene . Biochem. Biophys. Res. Commun. . 319 . 3 . 817–25 . 2004 . 15184056 . 10.1016/j.bbrc.2004.05.057 . etal.
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.

Notes and References

1. Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM . cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family . Cell . 85 . 6 . 829–39 . Aug 1996 . 8681378 . 10.1016/S0092-8674(00)81267-2 . 15805562 . free .
2. Byrd PJ, Stankovic T, McConville CM, Smith AD, Cooper PR, Taylor AM . Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11q22-23 . Genome Res . 7 . 1 . 71–5 . May 1997 . 9037604 . 10.1101/gr.7.1.71 . free .
3. Web site: Entrez Gene: CUL5 cullin 5.
4. Burnatowska-Hledin MA, Spielman WS, Smith WL . Expression cloning of an AVP-activated, calcium-mobilizing receptor from rabbit kidney medulla . Am J Physiol . 268 . 6 . F1198–210 . 1995 . 7611460 . 10.1152/ajprenal.1995.268.6.F1198. etal.
5. Burnatowska-Hledin M, Lazdins IB, Listenberger L . VACM-1 receptor is specifically expressed in rabbit vascular endothelium and renal collecting tubule . Am J Physiol . 276 . 2 Pt 2 . F199–209 . 1999 . 9950950 . 10.1152/ajprenal.1999.276.2.F199. etal.
6. Petroski MD, Deshaies RJ . Function and regulation of cullin-RING E3 ligases . Nature Reviews Molecular Cell Biology . 6 . 1 . 9–21 . 2005 . 15688063 . 10.1038/nrm1547 . 24159190 .
7. Feng L, Allen NS, Simo S, Cooper JA . Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical development . . 21 . 21 . 2717–30 . November 2007 . 17974915 . 2045127 . 10.1101/gad.1604207 .
8. Duda . David M . Borg Laura A . Scott Daniel C . Hunt Harold W . Hammel Michal . Schulman Brenda A . Sep 2008 . Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation . Cell . 134 . 6 . 995–1006 . United States. 18805092 . 10.1016/j.cell.2008.07.022 . 2628631 .
9. Ohta . T . Michel J J . Schottelius A J . Xiong Y . Apr 1999 . ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity . Mol. Cell . 3 . 4 . 535–41 . UNITED STATES. 1097-2765. 10230407 . 10.1016/S1097-2765(00)80482-7 . 19371828 . free .