TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

Young D. Yoo; Ju Youn Choi; Su Jae Lee; Jun S. Kim; Byung Re Min; Young I. Lee; Yoon Koo Kang

doi:10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z

TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

Young D. Yoo, Ju Youn Choi, Su Jae Lee, Jun S. Kim, Byung Re Min, Young I. Lee, Yoon Koo Kang

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G₁/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G₁ cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.

Original language	English
Pages (from-to)	512-517
Number of pages	6
Journal	International Journal of Cancer
Volume	83
Issue number	4
DOIs	https://doi.org/10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z
Publication status	Published - 1999

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z

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@article{61cddaa6abc8458796ec5a9247a9ffbb,

title = "TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells",

abstract = "Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.",

author = "Yoo, {Young D.} and Choi, {Ju Youn} and Lee, {Su Jae} and Kim, {Jun S.} and Min, {Byung Re} and Lee, {Young I.} and Kang, {Yoon Koo}",

year = "1999",

doi = "10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z",

language = "English",

volume = "83",

pages = "512--517",

journal = "International Journal of Cancer",

issn = "0020-7136",

publisher = "Wiley-Liss Inc.",

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TY - JOUR

T1 - TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

AU - Yoo, Young D.

AU - Choi, Ju Youn

AU - Lee, Su Jae

AU - Kim, Jun S.

AU - Min, Byung Re

AU - Lee, Young I.

AU - Kang, Yoon Koo

PY - 1999

Y1 - 1999

N2 - Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.

AB - Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.

UR - http://www.scopus.com/inward/record.url?scp=0032852135&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z

DO - 10.1002/(SICI)1097-0215(19991112)83:4<512::AID-IJC13>3.0.CO;2-Z

M3 - Article

C2 - 10508488

AN - SCOPUS:0032852135

SN - 0020-7136

VL - 83

SP - 512

EP - 517

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 4

ER -

TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

Abstract

ASJC Scopus subject areas

UN SDGs

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