2007 Fiscal Year Final Research Report Summary
Comprehensive analysis of TRIM family ubiquitin ligases
| Project/Area Number |
18390079
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
HATAKEYAMA Shigetsugu Hokkaido University, Graduate School of Medicine, Professor (70294973)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKIYAMA Tadasuke Hokkaido University, Graduate School of Medicine, Assistant Professor (20399819)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Ubiquitin / Proteasome / TRIM protein / Cancer / Ubiquitin ligase |
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| Research Abstract |
Ubiquitination is a versatile post-translational modification mechanism used by eukaryotic cells mainly to control protein levels through proteasome-mediated proteolysis. Ubiquitin conjugation is achieved by several enzymes that act in concert, a ubiquitin-protein ligase (E3). E3 is thought to be the component of the ubiquitin conjugation system that is most directly responsible for substrate recognition. Enzymes belonging to class E3 that have so far been identified include members of the HECT (homologous to E6-AP carboxyl terminus), RING-finger and U-box families of proteins. So far; we have published many articles about ubiquitination and oncogenesis.
Tripartite motif (TRIM) proteins are characterized by the presence of a RING finger, one or two zinc-binding motifs named B-boxes and an associated coiled-coil region (BBRC357: 245, 2007; Mal Cell Biochem 307, 73, 2008; Mol Immunol 45 2045, 2008, Cancer Res, in press).
We found that the putative E3 ubiquitin ligase TRIM68, which is prefe
… More
rentially expressed in prostate cancer cells, interacts with androgen receptor (AR) and enhances transcriptional activity of the AR in the presence of dihydrotestosterone (DHT). Overexpression of TRIM68 in prostate cancer cells caused an increase in secretion of prostate-specific antigen (PSA), one of the most reliable diagnostic markers for prostate cancer. Moreover, we showed that TRIM68 expression is significantly upregulated in human prostate cancers (Cancer Res, in press).
Furthermore, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor gene and a cell migration inhibitor Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity and cell motility In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) (cDDP) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis and resistance to anti-cancer drugs. Less
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[Journal Article] Ubiquitylation of s-COP by PIRH2 and regulation of the secretion of PSA.2007
Author(s)
Maruyama, S., Miyajima, N., Bohgaki, M., Tsukiyama, T., Shigemura, M., Nonomura, K. and Hatakevama, S.
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Journal Title
Neurosci. Lett 411
Pages: 228-232
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] APS-mediated Ubiquitination of the Insulin Receptor Enhances its Internalization, but does not Induce its Degradation.2007
Author(s)
Kishi, K., Mawatari, K., Sakai-Wakamatsu, K., Yuasa, T., Wang, M., Ogura-Sawa, M., Nakaya, Y., Hatakeyama, S. and Ebina, Y.
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Journal Title
Endocr. J 54
Pages: 77-88
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ligand-dependent transcription of estrogen receptor a is mediated by the ubiquitin ligase EFP.2007
Author(s)
Nakajima, A., Maruyama, S., Bohgaki, M., Miyajima, N., Tsukiyama, T., Sakuragi, N. and Hatakevama, S.
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Journal Title
Biochem. Biophys. Res. Commun 357
Pages: 245-251
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Elmol inhibits ubiquitylation of Dock180.2006
Author(s)
Makino, Y., Tsuda, M., Ichihara, S., Watanabe, T., Sawa, H., Nagashima, K., Hatakeyama, S. and Tanaka, S
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Journal Title
J. Cell Sci 119
Pages: 923-932
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Degradation of Tobl mediated by2006
Author(s)
Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., Oda, T., Hatakevama S., Nakayama, K-i., Yamamoto, T., Konno, H. and Kitagawa, M.
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Journal Title
Cancer Res 66
Pages: 8477-8483
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Ubiquitin-mediated regulation of coatomer protein complex, subunit epsilon byARNIP/Pirh2.2007
Author(s)
Maruyama S., Miyajima N., Sato T., Kashiwagi A., Satoshi N., Abe, T., Sazawa A., Harabayashi T., Shinohara N., Hatakevama. S., Nonomura K
Organizer
Annual Meeting of the American Urological Association Education and Research Inc
Place of Presentation
Anaheim
Year and Date
20070519-24
Description
「研究成果報告書概要(欧文)」より
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[Presentation] GdX, an X-linked ubiuitin-like modifier, is conjugated to cyclin F and regulates mitotic exit.2006
Author(s)
Ishida, N., Hatakeyama, S.. Iemura, S., Natsume, T., Nakayama, K. and Nakayama, KI.
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto
Year and Date
20060618-23
Description
「研究成果報告書概要(欧文)」より
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