Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating Kinase (CAK)

Mandal, Mahitosh ; Bandyopadhyay, Debdutta ; Goepfert, Thea M. ; Kumar, Rakesh (1998) Interferon-induces expression of cyclin-dependent kinase-inhibitors p21WAF1 and p27Kip1 that prevent activation of cyclin-dependent kinase by CDK-activating Kinase (CAK) Oncogene, 16 (2). pp. 217-225. ISSN 0950-9232

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Official URL: https://www.nature.com/articles/1201529

Related URL: http://dx.doi.org/10.1038/sj.onc.1201529

Abstract

To understand the mechanism of Interferon (IFN)-mediated suppression of cell cycle progression, we have earlier shown that IFN-α enhances the expression of underphosphorylated retinoblastoma protein by inhibiting the cyclin-dependent kinase-2 (CDK-2) activity (Kumar and Atlas, Proc. Natl. Acad. Sci. 89, 6599 – 6603, 1992; Zhang and Kumar, Biochem. Biophysi. Res. Comm., 200, 522 – 528, 1994). In the studies presented here, we investigated the mechanism of inhibition of CDKs in IFN-treated cells by delineating the potential role(s) of CDK-inhibitors (CKIs) and CDK-activating Kinase (CAK). We report that IFN-α inhibits the H-1 kinase activity associated with CDK-4 or CDK-2 due to induction of expression of CDK-inhibitor p21WAF1 (but not p27Kip1) as its immunodepletion from IFN-treated extracts restored the CDK-associated H-1 kinase activity. In addition, we also show that IFN-γ induces expression of CDK-inhibitors p21WAF1 and p27Kip1) and inhibited the H-1 kinase activity associated with CDK-2 or CDK-4. The observed IFN-γ-mediated inhibition of CDK-2 and CDK-4 kinase activity was due to enhanced interactions with p21WAF1 and p27Kip1), respectively. We also demonstrated that IFN-induced CKIs prevent CAK from activating the CDK-2 as immunodepletion of induced CKIs from the inhibitory extracts resulted in the restoration of CAK-mediated activation of CDK-2.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:Interferons; Cell Cycle; CDK; CDK-inhibitors; CDK-activating Kinase
ID Code:112893
Deposited On:08 May 2018 11:26
Last Modified:08 May 2018 11:26

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