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The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta.

Publication ,  Journal Article
Hu, PP; Shen, X; Huang, D; Liu, Y; Counter, C; Wang, XF
Published in: J Biol Chem
December 10, 1999

Transforming growth factor-beta (TGF-beta)can induce the cyclin-dependent kinase inhibitors p21 and p15 in a variety of cell types. We have shown previously that Smad3 is required for the growth inhibitory activity of TGF-beta, whereas overexpression of Smads is not sufficient to activate the expression of p21 in HaCaT cells. These data suggest that an additional signaling pathway may be involved in stimulating p21 in HaCaT cells. Given the recent finding that the mitogen-activated protein kinase (MAPK) pathway can cause p21 induction and arrest cells, we examined the involvement of this pathway for p21 and p15 induction by TGF-beta. We found that TGF-beta can regulate the MAPK pathway, leading to the increased transactivation ability of transcription factor Elk. Constitutively active components in the MAPK pathway activate p21 expression, and inhibitors or dominant negative constructs for the MAPK pathway significantly decrease p21 induction by TGF-beta. Both constitutively active MEK and inhibitors for MEK have no effect on Smad activity, including DNA binding, localization, and interaction with coactivator p300/CBP. These findings suggest that the MAPK pathway may be an independent pathway that is involved in p21 and p15 induction by TGF-beta.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 10, 1999

Volume

274

Issue

50

Start / End Page

35381 / 35387

Location

United States

Related Subject Headings

  • ras Proteins
  • Transforming Growth Factor beta
  • Transfection
  • Signal Transduction
  • Rifabutin
  • Recombinant Fusion Proteins
  • Quinones
  • Proto-Oncogene Proteins c-raf
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
 

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Hu, P. P., Shen, X., Huang, D., Liu, Y., Counter, C., & Wang, X. F. (1999). The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta. J Biol Chem, 274(50), 35381–35387. https://doi.org/10.1074/jbc.274.50.35381
Hu, P. P., X. Shen, D. Huang, Y. Liu, C. Counter, and X. F. Wang. “The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta.J Biol Chem 274, no. 50 (December 10, 1999): 35381–87. https://doi.org/10.1074/jbc.274.50.35381.
Hu PP, Shen X, Huang D, Liu Y, Counter C, Wang XF. The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta. J Biol Chem. 1999 Dec 10;274(50):35381–7.
Hu, P. P., et al. “The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta.J Biol Chem, vol. 274, no. 50, Dec. 1999, pp. 35381–87. Pubmed, doi:10.1074/jbc.274.50.35381.
Hu PP, Shen X, Huang D, Liu Y, Counter C, Wang XF. The MEK pathway is required for stimulation of p21(WAF1/CIP1) by transforming growth factor-beta. J Biol Chem. 1999 Dec 10;274(50):35381–35387.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 10, 1999

Volume

274

Issue

50

Start / End Page

35381 / 35387

Location

United States

Related Subject Headings

  • ras Proteins
  • Transforming Growth Factor beta
  • Transfection
  • Signal Transduction
  • Rifabutin
  • Recombinant Fusion Proteins
  • Quinones
  • Proto-Oncogene Proteins c-raf
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases