• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Regulation of degradation of p27Kip1, one of CDK inhibitory protein, for cancer therapy

Research Project

Project/Area Number 10558105
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional biochemistry
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KITAGAWA Masatoshi  Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 助教授 (50294971)

Co-Investigator(Kenkyū-buntansha) NAKAYAMA Keiichi  Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (80291508)
HATAKEYAMA Shigetsugu  Medical Institute of Bioregulation, Kyushu University, Research Assoc., 生体防御医学研究所, 助手 (70294973)
NAKAYAMA Keiko  Medical Institute of Bioregulation, Kyushu University, Assoc. Prof., 生体防御医学研究所, 助教授 (60294972)
HIRAI Aizan  Chiba Prefectural Togane Hospital, President, 院長
Project Period (FY) 1998 – 1999
Keywordsp27ィイD1Kip1ィエD1 / ubiquitination / proteasome / lung cancer / cyclin-dependent kinase
Research Abstract

It has been reported that the cyclin dependent kinase inhibitory proteins (CDK inhibitor) , such as p27ィイD1Kip1ィエD1 negatively regulates the G1-CDK activity in normal cells. In most cancer cells, up-regulation of G1-cyclin dependent kinase (G1-CDK) activity contributes in their malignant growth. First of all, we study the expression of p27ィイD1Kip1ィエD1 in human lung cancer using immunohistoichemistry. We found that p27ィイD1Kip1ィエD1 labeling index was decreased and p27ィイD1Kip1ィエD1 degradation activity was up-regulated in cancerious lung tissues, compared with nonneoplastic lung tissues. Therefore, it is important to study the mechanisms of p27ィイD1Kip1ィエD1 degradation. In the next study, we found that p27ィイD1Kip1ィエD1 was eliminated by two independent mechanisms, ubiquitin-mediated degradation and ubiquitin-independent processing. These tow activity was significantly high during progression from G1 to S phase. These finding suggested that inhibitor of p27ィイD1Kip1ィエD1 degradation is a potential drug for cancer therapy.

  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Noguchi, Y.: "Newly synthesized Rho A, not Ra is isoprenylated and translocated to membrane coincident with progression of the G1 to Sphase of growth stimulatedral FRTL-5 cells"J. Bio. Chem.. 273. 3649-3653 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kwwana, H: "Role p27Kip1 and cyclin-dependent kinase 1 in the proliferation of non-small cell lung cancer."Am. J. Pathol.. 153. 505-513 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, T.: "Acyivation of cyclin-dependent kinase 2(Cdk2) in growth-stimulated rat astrocyles. Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression"J. Biol. Chem.. 273. 26772-26778 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagata, M: "Cell cycle regulation and differentiation in the human podocyte linage."Am. J. Pathol.. 153. 1511-1520 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamasaki, A.: "Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene"J. Exp. Med. 188. 1985-1992 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe, Y.: "Prb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk)2 and Cdk4 in retinoic acid-induced neuronal differentialtion of P19 cells"Brain Res..

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitagawa, M.,: "An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of b-catenin."EMBO J. 8. 2401-2410 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shirane, M.: "Common pathway for the ubiquitination of 1kBa, ikBb, and ikBe mediated by the F-box protein FWD1"j. Biol. Chem.. 274. 28169-28174 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hatakeyama, S.: "Ubiquitin-dependent degradation of ikBa is mediated by a ubiquitin ligase Skp 1/Cul 1/F-box portein FWD1"Proc. Natl. Acad. Sci. USA. 96. 11364-11369 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shirane, M: "Down-regulation of p27 Kp1 by two mechanizms, ubiquitin-mediated degradation and site-specific cleavage."J. Biol. Chem.. 274. 13886-13893 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Lorick, K: "RING fingers mediate ubiquitin-conjugating enzyme (E2) -dependent ubiquitination"Proc. Natl. Acad. Sci. USA. 96. 11364-11369 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hattori, K.: "Molecular dissection of the interaactions among lkBa, FWD1 and Skp1 required for ubiquitin-mediated protelysis of 1kBa"J. Biol. Chem.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noguchi, Y., Nakamura, S., Yasuda, T., Kitagawa, M., Kohn, L. D., Saito, Y. and Hirai, A.: "Newly synthesized Pho A, not Ras is isoprenylated and translocated to membranes coincident with progression of the G1 to S phase of growth stimulated rat FRTL-5 cells"J. Biol. Chem.. 273. 3649-3653 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawana, H., Tamaru, J., Tanaka, T., Hirai, A., Saito, Y., Kitagawa, M., Mikita A., Harigaya, K. and Kuriyama, T.: "Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer"Am. J. Pathol.. 153. 505-513 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka, T., Tatsuno, I., Noguchi, Y., Uchida, D., Oeda, T., Narumiya, S., Yasuda, T., Higashi, H., Kitagawa, M., Nakayama, K.-I, Saito, Y. and Hirai., A.: "Activation of cyclin-dependent kinase 2 (Cdk2) in growth-stimulated rat astrocytes. Geranylgeranylated Rho small GTPase(s) are essential for the induction of cyclin E gene expression"J. Biol. Chem.. 273. 26772-26778 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagata, M., Nakayama, K.-I, Terada, Y., Hoshi, S. and Watanabe, T.: "Cell cycle regulation and differentiation in the human podocyte lineage"Am. J. Pathol.. 153. 1511-1520 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamasaki, A., Sendo, F., Nakayama, K., Ishida, N., Negishi, I., Nakayama, K,-I, and Hatakeyama, S.: "Accelerated neutrophil apoptosis in mice lacking A1-a, a sybtype of the bcl-2-related A1 gene"J. Exp. Med.. 188. 1985-1992 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe, Y., Watanabe, T., Kitagawa, M., Taya, Y., Nakayama, K-I, Motoyama, N.: "pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 2 and Cdk4 in retinoic acid-induced neuronal differential of P19 cells"Brain Res.. 842. 342-350 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, M., Hatakeyatam, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., Nakamichi, I., Kikuchi, A., Nakayama, K.-I., and Nakayama, K.: "An F-box protein , FWD1, mediates ubiquitin-dependent proteolysis of β-catenin"EMBO J.. 18. 2401-2410 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shirane, M., Harumiya, Y., Ishida, N., Hirai, A., Miyamoto, C., Hatakeyama, S., Nakayama, K-I., Kitagawa, M.: "Down-regulation of p27ィイD1Kip1ィエD1 by two mechanisms, ubiquitin-madeiated degradation and proteolytic processing"J. Biol. Chem.. 274. 13886-13893 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hatakeyama, S., Kitagawa, M., Nakayama, K., Shirane, M., Matsumoto, M., Hattori, K., Higashi, H., Nakano, H., Okumura, K., Onoe, K., Good, R. A., and Nakayama, K.-I.: "ubiquitin-dependent degradation of 1κBα is mediated by a ubiquitin ligase Skp1/Cul1.F-box protein FWD1"Proc. Natl. Acad. Sci. USA. 96. 3856-3863 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shirane, M., Hatakeyama, S., Hattori, K., Nakayama, K., and Nakayama, K.-I.: "Common pathway foe the ubiquitination of 1κBα, 1κBβ, and 1κBε mediated by the F-box protein FWD1"J. Biol. Chem.. 274. 28169-28174 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Lorick, K. L., Jensen, J. P., Fang, S. Y., Ong, A. M. Hatameyama, S., Weissman, A. M.: "RING fingers mediate ubiquinitin-conjugating enzyme (E2)-dependent ubiquitination"Proc. Natl. Acad. Sci. USA. 96. 11364-11369 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hattori, K., Hatakeyama, S., Shirane, M., Matsumoto, M., Nakayama, K.-I.: "Molecular dissection of the interactions among 1κBα, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of 1κBα"J. Biol. Chem.. 274. 29641-29647 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi