HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 40, 33945-33952, October 7, 2005

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 280/40/33945    most recent M506206200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kwak, Y.-T. Articles by Verma, U. N. Search for Related Content PubMed PubMed Citation Articles by Kwak, Y.-T. Articles by Verma, U. N. Social Bookmarking                      What's this?

IB Kinase Regulates Subcellular Distribution and Turnover of Cyclin D1 by Phosphorylation^*

From the Department of Medicine, Division of Hematology/Oncology, Utah Southwestern Medical Center at Dallas, Dallas, Texas 75390

IB kinases (IKKs), IKK and IKK, with a regulatory subunit IKK/NEMO constitute a high molecular weight IKK complex that regulates NF-B activity. Although IKK and IKK share structural and biochemical similarities, IKK has been shown to have distinct biological roles. Here we show that IKK plays a critical role in regulating cyclin D1 during the cell cycle. Analysis of IKK^-/- mouse embryo fibroblast cells showed that cyclin D1 is overexpressed and localized in the nucleus compared with parental mouse embryo fibroblasts. IKK associates with and phosphorylates cyclin D1. Analysis on cyclin D1 mutants demonstrated that IKK phosphorylates cyclin D1 at Thr²⁸⁶. Reconstitution of IKK in knockout cells leads to nuclear export and increased degradation of cyclin D1. Further, RNAi-mediated knockdown of IKK results in similar changes as observed in IKK^-/- cells. These results suggest a novel role of IKK in regulating subcellular localization and proteolysis of cyclin D1 by phosphorylation of cyclin D1 at Thr²⁸⁶, the same residue earlier found to be a target for glycogen synthase kinase-3-induced phosphorylation.

Received for publication, June 7, 2005 , and in revised form, August 15, 2005.

^* This work was supported by Public Health Service Grant R01 AI041860 (to U. N. V.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Medicine, Division of Hematology/Oncology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390. Tel.: 214-648-7416; Fax: 214-648-4152; E-mail: udit.verma{at}utsouthwestern.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Wei, H.-C. Yang, H.-C. Chuang, J. Yang, S. K. Kulp, P.-J. Lu, M.-D. Lai, and C.-S. Chen A Novel Mechanism by Which Thiazolidinediones Facilitate the Proteasomal Degradation of Cyclin D1 in Cancer Cells J. Biol. Chem., September 26, 2008; 283(39): 26759 - 26770. [Abstract] [Full Text] [PDF]

				D.-F. Lee and M.-C. Hung Advances in Targeting IKK and IKK-Related Kinases for Cancer Therapy Clin. Cancer Res., September 15, 2008; 14(18): 5656 - 5662. [Abstract] [Full Text] [PDF]

				F. Takahashi-Yanaga, J. Mori, E. Matsuzaki, Y. Watanabe, M. Hirata, Y. Miwa, S. Morimoto, and T. Sasaguri Involvement of GSK-3beta and DYRK1B in Differentiation-inducing Factor-3-induced Phosphorylation of Cyclin D1 in HeLa Cells J. Biol. Chem., December 15, 2006; 281(50): 38489 - 38497. [Abstract] [Full Text] [PDF]

				Z. Tu, S. Prajapati, K.-J. Park, N. J. Kelly, Y. Yamamoto, and R. B. Gaynor IKK{alpha} Regulates Estrogen-induced Cell Cycle Progression by Modulating E2F1 Expression J. Biol. Chem., March 10, 2006; 281(10): 6699 - 6706. [Abstract] [Full Text] [PDF]