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Gene Review

COPS5  -  COP9 signalosome subunit 5

Homo sapiens

Synonyms: COP9 signalosome complex subunit 5, CSN5, JAB1, Jun activation domain-binding protein 1, MOV-34, ...
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Disease relevance of COPS5


High impact information on COPS5

  • Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity [5].
  • We suggest that signalling through the LFA-1 integrin may affect c-Jun-driven transcription by regulating JAB1 nuclear localization [5].
  • MIF inhibits Jab1- and stimulus-enhanced AP-1 activity, but does not interfere with the induction of the transcription factor NFkappaB [6].
  • Moreover, in anergic cells, p27kip1 associates with the c-Jun co-activator JAB1, resulting in defective transactivation of AP-1 and interleukin 2 transcription [7].
  • Jab1 activates c-Jun amino-terminal kinase (JNK) activity and enhances endogenous phospho-c-Jun levels, and MIF inhibits these effects [6].

Biological context of COPS5


Anatomical context of COPS5


Associations of COPS5 with chemical compounds

  • On the cellular level, Jab1 knock-down cells exhibited reduced mitotic arrest upon exposure to nocodazole, resulting in cellular resistance to the drug [10].
  • Amino acids 50-65 and Cys 60 of MIF are important for Jab1 binding and modulation [6].
  • Inhibition of Bcr-Abl kinase by STI571 induced G1 arrest and caused a recovery of the p27 level with reduction of the small Jab1 complex from the cytoplasm [11].
  • Here we show that Bcr-Abl tyrosine kinase facilitates the down-regulation of p27 by modulating complex formation of Jab1/CSN through the mitogen-activated protein (MAP) kinase and phosphatidylinositol 3 (PI3) kinase signaling pathways [11].
  • Depleting Jab1/CSN5 by antisense oligonucleotide and treating cells with the CSN-associated kinase inhibitor, curcumin, inhibited topo IIalpha degradation induced by glucose starvation [12].

Physical interactions of COPS5

  • Furthermore, the Jab1-binding domain is also necessary for the enhanced tumorigenicity conferred by S100A7 expression in murine xenograft tumors in vivo [2].
  • As visualized by electron microscopy, p53 binds with high affinity to the native CSN complex. p53 interacts via its N-terminus with CSN subunit 5/Jab1 as shown by far-western and pull-down assays [13].
  • Jab1 interacts directly with Smad4 and induces its ubiquitylation for degradation [14].
  • In vitro, JAB1 specifically stabilizes complexes of c-Jun or JunD with AP-1 sites and does not affect binding of either JunB or v-Jun [15].
  • We show here that Jab1 interacts in vivo with nuclear receptor binding protein (NRBP), an evolutionarily conserved adapter protein with a kinase-like domain [16].

Enzymatic interactions of COPS5

  • The isolated JAB1-containing particle has kinase activity that phosphorylates IkappaBalpha, the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino-terminal activation domain of c-Jun [17].

Regulatory relationships of COPS5

  • The inhibition of endogenous Jab1/CSN5 expression by small interfering RNA (siRNA) induces Smad7 expression [18].
  • Jab1 promotes degradation of the cyclin-dependent kinase inhibitor p27(Kip1) by transportation from the nucleus to the cytoplasm [11].
  • Taken together, our results suggest that HER-2/neu transcriptionally activates Jab1 expression to promote proliferation of breast cancer cells [19].
  • Our results indicate that Jab1 is overexpressed in HCC and PPARgamma ligands may suppress Jab1 to inhibit the proliferation of HCC cells [20].

Other interactions of COPS5


Analytical, diagnostic and therapeutic context of COPS5


  1. Jun activation domain-binding protein 1 expression in malignant lymphoma of the thyroid: its linkage to degree of malignancy and p27 expression. Ito, Y., Yoshida, H., Matsuzuka, F., Matsuura, N., Nakamura, Y., Nakamine, H., Kakudo, K., Kuma, K., Miyauchi, A. Anticancer Res. (2003) [Pubmed]
  2. The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Emberley, E.D., Niu, Y., Curtis, L., Troup, S., Mandal, S.K., Myers, J.N., Gibson, S.B., Murphy, L.C., Watson, P.H. Cancer Res. (2005) [Pubmed]
  3. Interaction and colocalization of PGP9.5 with JAB1 and p27(Kip1). Caballero, O.L., Resto, V., Patturajan, M., Meerzaman, D., Guo, M.Z., Engles, J., Yochem, R., Ratovitski, E., Sidransky, D., Jen, J. Oncogene (2002) [Pubmed]
  4. Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas. Shintani, S., Li, C., Mihara, M., Hino, S., Nakashiro, K., Hamakawa, H. Oncology (2003) [Pubmed]
  5. Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Bianchi, E., Denti, S., Granata, A., Bossi, G., Geginat, J., Villa, A., Rogge, L., Pardi, R. Nature (2000) [Pubmed]
  6. Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Kleemann, R., Hausser, A., Geiger, G., Mischke, R., Burger-Kentischer, A., Flieger, O., Johannes, F.J., Roger, T., Calandra, T., Kapurniotu, A., Grell, M., Finkelmeier, D., Brunner, H., Bernhagen, J. Nature (2000) [Pubmed]
  7. p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes. Boussiotis, V.A., Freeman, G.J., Taylor, P.A., Berezovskaya, A., Grass, I., Blazar, B.R., Nadler, L.M. Nat. Med. (2000) [Pubmed]
  8. Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1. Hwang, C.Y., Ryu, Y.S., Chung, M.S., Kim, K.D., Park, S.S., Chae, S.K., Chae, H.Z., Kwon, K.S. Oncogene (2004) [Pubmed]
  9. Expression of cyclin-dependent kinase inhibitor p27/Kip1 and AP-1 coactivator p38/Jab1 correlates with differentiation of embryonal rhabdomyosarcoma. Tsuchida, R., Miyauchi, J., Shen, L., Takagi, M., Tsunematsu, Y., Saeki, M., Honna, T., Yamada, S., Teraoka, H., Kato, J.Y., Mizutani, S. Jpn. J. Cancer Res. (2002) [Pubmed]
  10. Jun activation domain-binding protein 1 is required for mitotic checkpoint activation via its involvement in hyperphosphorylation of 53BP1. Kwak, H.J., Kim, S.H., Yoo, H.G., Park, S.H., Lee, C.H. J. Cancer Res. Clin. Oncol. (2005) [Pubmed]
  11. The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression. Tomoda, K., Kato, J.Y., Tatsumi, E., Takahashi, T., Matsuo, Y., Yoneda-Kato, N. Blood (2005) [Pubmed]
  12. Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5. Yun, J., Tomida, A., Andoh, T., Tsuruo, T. J. Biol. Chem. (2004) [Pubmed]
  13. COP9 signalosome-specific phosphorylation targets p53 to degradation by the ubiquitin system. Bech-Otschir, D., Kraft, R., Huang, X., Henklein, P., Kapelari, B., Pollmann, C., Dubiel, W. EMBO J. (2001) [Pubmed]
  14. Jab1 antagonizes TGF-beta signaling by inducing Smad4 degradation. Wan, M., Cao, X., Wu, Y., Bai, S., Wu, L., Shi, X., Wang, N., Cao, X. EMBO Rep. (2002) [Pubmed]
  15. A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. Claret, F.X., Hibi, M., Dhut, S., Toda, T., Karin, M. Nature (1996) [Pubmed]
  16. Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity. Wang, H., Sun, X., Luo, Y., Lin, Z., Wu, J. FEBS Lett. (2006) [Pubmed]
  17. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. Seeger, M., Kraft, R., Ferrell, K., Bech-Otschir, D., Dumdey, R., Schade, R., Gordon, C., Naumann, M., Dubiel, W. FASEB J. (1998) [Pubmed]
  18. Jab1/CSN5, a component of the COP9 signalosome, regulates transforming growth factor beta signaling by binding to Smad7 and promoting its degradation. Kim, B.C., Lee, H.J., Park, S.H., Lee, S.R., Karpova, T.S., McNally, J.G., Felici, A., Lee, D.K., Kim, S.J. Mol. Cell. Biol. (2004) [Pubmed]
  19. HER-2/neu transcriptionally activates Jab1 expression via the AKT/beta-catenin pathway in breast cancer cells. Hsu, M.C., Chang, H.C., Hung, W.C. Endocr. Relat. Cancer (2007) [Pubmed]
  20. Overexpression of Jab1 in hepatocellular carcinoma and its inhibition by peroxisome proliferator-activated receptor{gamma} ligands in vitro and in vivo. Hsu, M.C., Huang, C.C., Chang, H.C., Hu, T.H., Hung, W.C. Clin. Cancer Res. (2008) [Pubmed]
  21. JAB1 interacts with both the progesterone receptor and SRC-1. Chauchereau, A., Georgiakaki, M., Perrin-Wolff, M., Milgrom, E., Loosfelt, H. J. Biol. Chem. (2000) [Pubmed]
  22. Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1). Kouvaraki, M.A., Rassidakis, G.Z., Tian, L., Kumar, R., Kittas, C., Claret, F.X. Cancer Res. (2003) [Pubmed]
  23. Jab1, a novel protease-activated receptor-2 (PAR-2)-interacting protein, is involved in PAR-2-induced activation of activator protein-1. Luo, W., Wang, Y., Hanck, T., Stricker, R., Reiser, G. J. Biol. Chem. (2006) [Pubmed]
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