COPS6 explained

COP9 signalosome complex subunit 6 is a protein that in humans is encoded by the COPS6 gene.^[1]

Function

The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr.^[2]

Interactions

COPS6 has been shown to interact with EIF3S6.^[3]

Further reading

• Wolf DA, Zhou C, Wee S . The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? . Nat. Cell Biol. . 5 . 12 . 1029–33 . 2004 . 14647295 . 10.1038/ncb1203-1029 . 37458780 .
• Muthumani K, Choo AY, Premkumar A, Hwang DS, Thieu KP, Desai BM, Weiner DB . Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism . Cell Death Differ. . 12 . 962–70 . 2006 . Suppl 1 . 15832179 . 10.1038/sj.cdd.4401583 . free .
• Mittmeyer HJ . [Distribution pattern of rigor mortis in various joint regions] . Beitr. Gerichtl. Med. . 33 . 85–96 . 1976 . 1222062 .
• He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR . Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity . J. Virol. . 69 . 11 . 6705–11 . 1995 . 7474080 . 189580 . 10.1128/JVI.69.11.6705-6711.1995.
• Re F, Braaten D, Franke EK, Luban J . Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B . J. Virol. . 69 . 11 . 6859–64 . 1995 . 7474100 . 189600 . 10.1128/JVI.69.11.6859-6864.1995.
• Di Marzio P, Choe S, Ebright M, Knoblauch R, Landau NR . Mutational analysis of cell cycle arrest, nuclear localization and virion packaging of human immunodeficiency virus type 1 Vpr . J. Virol. . 69 . 12 . 7909–16 . 1996 . 7494303 . 189735 . 10.1128/JVI.69.12.7909-7916.1995.
• Jowett JB, Planelles V, Poon B, Shah NP, Chen ML, Chen IS . The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle . J. Virol. . 69 . 10 . 6304–13 . 1995 . 7666531 . 189529 . 10.1128/JVI.69.10.6304-6313.1995.
• Zhao LJ, Mukherjee S, Narayan O . Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein . J. Biol. Chem. . 269 . 22 . 15577–82 . 1994 . 10.1016/S0021-9258(17)40719-8 . 8195203 . free .
• Poon B, Jowett JB, Stewart SA, Armstrong RW, Rishton GM, Chen IS . Human immunodeficiency virus type 1 vpr gene induces phenotypic effects similar to those of the DNA alkylating agent, nitrogen mustard . J. Virol. . 71 . 5 . 3961–71 . 1997 . 9094673 . 191548 . 10.1128/JVI.71.5.3961-3971.1997.
• Asano K, Vornlocher HP, Richter-Cook NJ, Merrick WC, Hinnebusch AG, Hershey JW . Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly . J. Biol. Chem. . 272 . 43 . 27042–52 . 1997 . 9341143 . 10.1074/jbc.272.43.27042 . free .
• Mahalingam S, Ayyavoo V, Patel M, Kieber-Emmons T, Kao GD, Muschel RJ, Weiner DB . HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle . Proc. Natl. Acad. Sci. U.S.A. . 95 . 7 . 3419–24 . 1998 . 9520381 . 19851 . 10.1073/pnas.95.7.3419 . 1998PNAS...95.3419M . free .
• Seeger M, Kraft R, Ferrell K, Bech-Otschir D, Dumdey R, Schade R, Gordon C, Naumann M, Dubiel W . A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits . FASEB J. . 12 . 6 . 469–78 . 1998 . 9535219 . 10.1096/fasebj.12.6.469. free . 25424324 .
• Wei N, Tsuge T, Serino G, Dohmae N, Takio K, Matsui M, Deng XW . The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex . Curr. Biol. . 8 . 16 . 919–22 . 1998 . 9707402 . 10.1016/S0960-9822(07)00372-7 . 13873982 . free . 1998CBio....8..919W .
• Elder RT, Yu M, Chen M, Edelson S, Zhao Y . Cell cycle G2 arrest induced by HIV-1 Vpr in fission yeast (Schizosaccharomyces pombe) is independent of cell death and early genes in the DNA damage checkpoint . Virus Res. . 68 . 2 . 161–73 . 2000 . 10958988 . 10.1016/S0168-1702(00)00167-2 .
• Ramanathan MP, Ayyavoo V, Weiner DB . Choice of expression vector alters the localization of a human cellular protein . DNA Cell Biol. . 20 . 2 . 101–5 . 2001 . 11244567 . 10.1089/104454901750070300 .
• Bech-Otschir D, Kraft R, Huang X, Henklein P, Kapelari B, Pollmann C, Dubiel W . COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system . EMBO J. . 20 . 7 . 1630–9 . 2001 . 11285227 . 145508 . 10.1093/emboj/20.7.1630 .
• Lyapina S, Cope G, Shevchenko A, Serino G, Tsuge T, Zhou C, Wolf DA, Wei N, Shevchenko A, Deshaies RJ . Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome . Science . 292 . 5520 . 1382–5 . 2001 . 11337588 . 10.1126/science.1059780 . 2001Sci...292.1382L . 14224920 .
• Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y . HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25 . Virology . 287 . 2 . 359–70 . 2001 . 11531413 . 10.1006/viro.2001.1007 . free .
• Hrimech M, Yao XJ, Branton PE, Cohen EA . Retraction . EMBO J. . 21 . 14 . 3918 . 2002 . 12110603 . 126131 . 10.1093/emboj/cdf420 .

Notes and References

1. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . 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 . Dec 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
2. Web site: Entrez Gene: COPS6 COP9 constitutive photomorphogenic homolog subunit 6 (Arabidopsis).
3. Hoareau Alves K, Bochard V, Réty S, Jalinot P . Association of the mammalian proto-oncoprotein Int-6 with the three protein complexes eIF3, COP9 signalosome and 26S proteasome . FEBS Lett. . 527 . 1–3 . 15–21 . Sep 2002 . 12220626 . 10.1016/S0014-5793(02)03147-2 . 39308598 . free .