An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant

Peng Ji, Hong Jiang, Katya Rekhtman, Joanna Bloom, Marina Ichetovkin, Michele Pagano, Liang Zhu

Research output: Contribution to journalArticle

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Abstract

It is believed that Rb blocks G1-S transition by inhibiting expression of E2F regulated genes. Here, we report that the effects of E2F repression lag behind the onset of G1 cell cycle arrest in timed Rb reexpression experiments. In comparison, kinase inhibitor p27Kip1 protein accumulates with a faster kinetics. Conversely, Rb knockout leads to faster p27 degradation. Rb interacts with the N terminus of Skp2, interferes with Skp2-p27 interaction, and inhibits ubiquitination of p27. Disruption of p27 function or expression of the Skp2 N terminus prevents Rb from causing G1 arrest. A full-penetrance, inactive Rb mutant fails to interfere with Skp2-p27 interaction but, interestingly, a partial-penetrance Rb mutant that is defective for E2F binding retains full activity in inhibiting Skp2-p27 interaction and can induce G1 cell cycle arrest with wild-type kinetics. These results identify an Rb-Skp2-p27 pathway in Rb function, which may be involved in inhibition of tumor progression.

Original languageEnglish (US)
Pages (from-to)47-58
Number of pages12
JournalMolecular Cell
Volume16
Issue number1
DOIs
StatePublished - Oct 8 2004

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G1 Phase Cell Cycle Checkpoints
Penetrance
Cell Cycle
Cyclin-Dependent Kinase Inhibitor p27
Ubiquitination
Phosphotransferases
Genes
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology

Cite this

An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. / Ji, Peng; Jiang, Hong; Rekhtman, Katya; Bloom, Joanna; Ichetovkin, Marina; Pagano, Michele; Zhu, Liang.

In: Molecular Cell, Vol. 16, No. 1, 08.10.2004, p. 47-58.

Research output: Contribution to journalArticle

Ji, Peng ; Jiang, Hong ; Rekhtman, Katya ; Bloom, Joanna ; Ichetovkin, Marina ; Pagano, Michele ; Zhu, Liang. / An Rb-Skp2-p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. In: Molecular Cell. 2004 ; Vol. 16, No. 1. pp. 47-58.
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