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Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect.

Publication ,  Journal Article
Li, CY; Suardet, L; Little, JB
Published in: J Biol Chem
March 10, 1995

Transforming growth factor-beta (TGF-beta) inhibits cell cycle progression of many types of human cells by arresting them in the G1 phase of the cell cycle. The arrest is mediated through interactions of various cyclin-dependent protein kinases (CDKs) and their inhibitors. We demonstrate that treatment with TGF-beta induces increased levels of WAF1/Cip1/p21, a potent inhibitor of various cyclin-CDK kinase activities, in two colon cancer cell lines (LS1034 and LS513), which are sensitive to TGF-beta-induced growth arrest. The induction in at least one of these cell lines (LS1034,p53-) is p53-independent. No WAF1 induction was observed after TGF-beta treatment in a third cell line (HT-29), which is completely insensitive to the cytoinhibitory effect of TGF-beta. In both LS513 and LS1034, WAF1 induction correlated with reduced cyclin E-associated kinase activity in vitro and suppression of the retinoblastoma susceptibility gene (Rb) protein phosphorylation in vivo. In addition, WAF1 was physically associated with cyclin E in the two sensitive cell lines. These results suggest that WAF1/Cip1/p21 is a mediator of cellular sensitivity to TGF-beta.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 10, 1995

Volume

270

Issue

10

Start / End Page

4971 / 4974

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Time Factors
  • Retinoblastoma Protein
  • RNA, Messenger
  • Protamine Kinase
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Point Mutation
  • Molecular Sequence Data
 

Citation

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Li, C. Y., Suardet, L., & Little, J. B. (1995). Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect. J Biol Chem, 270(10), 4971–4974. https://doi.org/10.1074/jbc.270.10.4971
Li, C. Y., L. Suardet, and J. B. Little. “Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect.J Biol Chem 270, no. 10 (March 10, 1995): 4971–74. https://doi.org/10.1074/jbc.270.10.4971.
Li CY, Suardet L, Little JB. Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect. J Biol Chem. 1995 Mar 10;270(10):4971–4.
Li, C. Y., et al. “Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect.J Biol Chem, vol. 270, no. 10, Mar. 1995, pp. 4971–74. Pubmed, doi:10.1074/jbc.270.10.4971.
Li CY, Suardet L, Little JB. Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect. J Biol Chem. 1995 Mar 10;270(10):4971–4974.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 10, 1995

Volume

270

Issue

10

Start / End Page

4971 / 4974

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Time Factors
  • Retinoblastoma Protein
  • RNA, Messenger
  • Protamine Kinase
  • Polymorphism, Genetic
  • Polymerase Chain Reaction
  • Point Mutation
  • Molecular Sequence Data