2000 Fiscal Year Annual Research Report

相互作用蛋白の遺伝子クローニングによる転写因子NF-κBの機能・制御系の解析

Research Project

Project/Area Number	12028230
Research Institution	Nagoya City University
Principal Investigator	岡本尚名古屋市立大学, 医学部, 教授 (40146600)
Keywords	転写 / NF-κB / コンプレッサー / TFIID / Groucho / FUS / TLS / RelA / アポトーシス
Research Abstract	誘導型の転写因子であるNF-κBは、蛋白間相互作用により活性調節を受けるとともにその機能を発現する。そこで、培養細胞からの生化学的方法による精製と酵母の遺伝系を用いたtwo-hybrid screening法によりNF-κBの主要サブユニットであるp65(RelA)と結合する一連の蛋白分子の同定と遺伝子クローニングを実施することにより、NF-κBの持つ種々の生物学的作用(転写活性化とアポトーシス抑制機構、など)の発現と調節機構に関わる未知の因子を同定することを目的に研究を進めた。その結果、今年度はp65の転写活性化ドメインに結合する因子として新たに転写コレプレッサー蛋白AES/TLE(Groucho related genes)とFUS/TKSを同定した。興味深いことに、FUS/TLSはAES/TLEによる転写抑制を解除し、また逆にAES/TLEはFUS/TLSによるNF-κBによる転写の活性化を抑えた。FUS/TLSはTAFII蛋白のひとつと考えられており転写基本因子TFIIDの一部を構成することから、AES/TLEによるコレプレッサー作用はNF-κBの転写活性化に関わる特定のTFIIDのリクルートを排除するためと考えられた。コレプレッサーとTAII蛋白の競合作用の発見は一般的な転写制御の立場からも重要な意義を持つ。また、すでにp65中央部分に結合する因子として同定した53BP2のアポトーシス誘導作用とそのがん細胞株での発現の意義を明らかにし、NF-κBのアポトーシス抑制機構には遺伝子発現を必要としない経路があることを確かめた。今後は、NF-κBを中心とする相互作用因子の同定をさらに進めるとともに、これらの分子間相互作用の全体像を細胞という限られた空間の中で解明していき、NF-κBの生物学的作用機構をさらに明らかにしたいと考えている。

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] Suzuki,M.: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-αor IL-1 β stimulated rheumatoid synovial fibroblasts."FEBS Lett.. 465. 23-27 (2000)
[Publications] Mori,T: "Aberrant overxpressin of 53BP2 mRNA in lung cancer cell lines."FEBS Lett.. 465. 124-128 (2000)
[Publications] Tetsuka,T.: "Inhibition of nuclear facter-κB-mediated transcription by association with the amino-terminal rnhancer of split (AES). a groucho-related protein lacking WD40 repeats."J.Biol.Chem.. 275. 4383-4390 (2000)
[Publications] Kameoka,M.: "Evidence for Regulation of NF-κB by Poly (ADP-ribose) Polymerase."Biochem.J.. 346. 641-649 (2000)
[Publications] Kajino,S.: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-κB."Oncogene. 19. 2233-2239 (2000)
[Publications] Kanazawa,S.: "Tat competes with C II TA for the binding to P-TEFb and blocks the exprression of MHC class II genes in HIV infection."Immunity. 12. 61-70 (2000)
[Publications] Okamoto,H.: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation."Virology. 270. 337-344 (2000)
[Publications] Kobayashi,K.: "Prevention of cancer metastasis by cimetidine through blocking the expression of E-selectin on endothelial cells."Cancer Res.. 60. 3978-3984 (2000)
[Publications] Okamoto,H.: "Inhibition of the RNA-dependent tansactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37."Virology. 272. 402-408 (2000)
[Publications] Nagaya,T.: "A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome."J.Clin Invest.. 106. 393-402 (2000)
[Publications] Okamoto,H: "Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator C II TA. Biochem."Biophys.Res.Commun.. 279. 494-499 (2000)
[Publications] Uranishi,H.: "Involvement of the pro-oncoprotein TLS (Translocated in liposarcoma) in nuclear factor -κB p65-mediated transcription as a coactivator."J.B.C.. (in press). (2001)
[Publications] Senoo,M: "Transcriptional dysregulation of the p/3L/p63/p51/p40/KET gene, which encodes both the tumor suppressor protein p51 and its dominant-negative form p73L, in human skin cancers."Br.J.Cancer. (in press).
[Publications] Okamoto,T.: "Role of thioredoxin in the redox regulation of gene expression in inflammatory diseases."Birkhauser Verlag Basel. 13 (2000)

2000 Fiscal Year Annual Research Report

相互作用蛋白の遺伝子クローニングによる転写因子NF-κBの機能・制御系の解析

Principal Investigator

岡本 尚 名古屋市立大学, 医学部, 教授 (40146600)

Research Products

[Publications] Suzuki,M.: "The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-αor IL-1 β stimulated rheumatoid synovial fibroblasts."FEBS Lett.. 465. 23-27 (2000)

[Publications] Mori,T: "Aberrant overxpressin of 53BP2 mRNA in lung cancer cell lines."FEBS Lett.. 465. 124-128 (2000)

[Publications] Tetsuka,T.: "Inhibition of nuclear facter-κB-mediated transcription by association with the amino-terminal rnhancer of split (AES). a groucho-related protein lacking WD40 repeats."J.Biol.Chem.. 275. 4383-4390 (2000)

[Publications] Kameoka,M.: "Evidence for Regulation of NF-κB by Poly (ADP-ribose) Polymerase."Biochem.J.. 346. 641-649 (2000)

[Publications] Kajino,S.: "Evidence that de novo protein synthesis is dispensable for anti-apoptotic effects of NF-κB."Oncogene. 19. 2233-2239 (2000)

[Publications] Kanazawa,S.: "Tat competes with C II TA for the binding to P-TEFb and blocks the exprression of MHC class II genes in HIV infection."Immunity. 12. 61-70 (2000)

[Publications] Okamoto,H.: "HIV-1 replication is inhibited by a pseudo-substrate peptide that blocks Tat transactivation."Virology. 270. 337-344 (2000)

[Publications] Kobayashi,K.: "Prevention of cancer metastasis by cimetidine through blocking the expression of E-selectin on endothelial cells."Cancer Res.. 60. 3978-3984 (2000)

[Publications] Okamoto,H.: "Inhibition of the RNA-dependent tansactivation and replication of human immunodeficiency virus type 1 by a fluoroquinoline derivative K-37."Virology. 272. 402-408 (2000)

[Publications] Nagaya,T.: "A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome."J.Clin Invest.. 106. 393-402 (2000)

[Publications] Okamoto,H: "Reciprocal modulation of transcriptional activities between HIV-1 Tat and MHC class II transactivator C II TA. Biochem."Biophys.Res.Commun.. 279. 494-499 (2000)

[Publications] Uranishi,H.: "Involvement of the pro-oncoprotein TLS (Translocated in liposarcoma) in nuclear factor -κB p65-mediated transcription as a coactivator."J.B.C.. (in press). (2001)

[Publications] Senoo,M: "Transcriptional dysregulation of the p/3L/p63/p51/p40/KET gene, which encodes both the tumor suppressor protein p51 and its dominant-negative form p73L, in human skin cancers."Br.J.Cancer. (in press).

[Publications] Okamoto,T.: "Role of thioredoxin in the redox regulation of gene expression in inflammatory diseases."Birkhauser Verlag Basel. 13 (2000)

岡本尚名古屋市立大学, 医学部, 教授 (40146600)