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Caspase-mediated Cdk2 activation is a critical step to execute transforming growth factor-β1-induced apoptosis in human gastric cancer cells

Cited 44 time in Web of Science Cited 51 time in Scopus
Authors
Kim, Sang Gyun; Kim, Se Nyun; Jong, Hyun-Soon; Kim, Noe Kyeong; Hong, Seung Hwan; Kim, Seong-Jin; Bang, Yung-Jue
Issue Date
2001-03
Citation
Oncogene, Vol.20 No.10, pp.1254-1265
Keywords
TGF-beta 1apoptosiscaspase-3cyclin-dependent kinase-2p21(cip1)p27(kip1)
Abstract
Although TGF-beta1, a growth inhibitor, is known to also induce apoptosis, the molecular mechanism of this apoptosis is largely undefined, Here, we identify the mechanism of TGF-beta1-induced apoptosis in SNU-16 human gastric cancer cells. Cell cycle and TUNEL analysis showed that, upon TGF-beta1 treatment, cells mere initially arrested at the G1 phase and then driven into apoptosis, Of note, caspase-3 was activated in accordance with TGF-beta1-induced G1 arrest, Activated caspase-3 is targeted to cleave p21(cip1), p27(kip1), and Rb, which play important roles in TGF-beta -induced G1 arrest, into;inactive fragments. Subsequently, Cdk2 was aberrantly activated due to the cleavage of p21 and p27, We found that the inhibition of Cdk2 activity efficiently blocks TGF-beta1-induced apoptosis, whereas it did; not prevent caspase-3 activation or the subsequent cleavage of target proteins, In contrast, the suppression of caspase-3 activity inhibited the cleavage of target proteins, the activation of Cdk2, and the induction of apoptosis. Taken together, our results suggest that activation of caspase-3 by TGF-beta1 may initiate the conversion from G1 cell cycle arrest to apoptosis via the cleavage of p21, p27 and Rb, which in turn causes Cdk2 activation and, most significantly, Cdk2 activation as a downstream effector of caspase is a critical step for the execution TGF-beta1-induced apoptosis.
ISSN
0950-9232
URI
https://hdl.handle.net/10371/173198
DOI
https://doi.org/10.1038/sj.onc.1204203
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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