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

J. Biol. Chem., Vol. 281, Issue 49, 37646-37651, December 8, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/49/37646    most recent M604476200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stoica, C. Articles by Hobman, T. C. Search for Related Content PubMed PubMed Citation Articles by Stoica, C. Articles by Hobman, T. C. Social Bookmarking                      What's this?

Interactions between the RNA Interference Effector Protein Ago1 and 14-3-3 Proteins

CONSEQUENCES FOR CELL CYCLE PROGRESSION^*

Cezar Stoica, Jon B. Carmichael, Henry Parker, Justin Pare, and Tom C. Hobman, Recipient of a Medical Scientist Award from the Alberta Heritage Foundation for Medical Research¹

From the Departments of Cell Biology and Medical Microbiology & Immunology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

The Argonaute family member Ago1 is required for formation of pericentric heterochromatin and small interfering RNA (siRNA)-mediated post-transcriptional gene silencing in the fission yeast Schizosaccharomyces pombe. In addition, we have recently demonstrated that Ago1 function is required for enactment of cell cycle checkpoints (Carmichael, J. B., Provost, P., Ekwall, K., and Hobman, T. C. (2004) Mol. Biol. Cell 15, 1425-1435). Here, we provide evidence that the amino terminus of Ago1 binds to proteins that function in cell cycle regulation including 14-3-3 proteins. Interestingly, the amino terminus of human Ago2, the endonuclease that cleaves siRNA-targeted mRNAs, was also demonstrated to bind 14-3-3 proteins. Overexpression of the Ago1 amino terminus in yeast resulted in cell cycle delay at the G₂/M boundary. Further investigation revealed that nuclear import of the mitosis-inducing phosphatase Cdc25 is inhibited by overexpression of the Ago1 amino terminus. Under these conditions, we found that the cyclin-dependent kinase Cdc2 is constitutively phosphorylated on tyrosine 15, thereby reducing the activity of this kinase, a situation that delays entry into mitosis. We hypothesize that 14-3-3 proteins are required for Argonaute protein functions in cell cycle and/or gene-silencing pathways.

Received for publication, May 10, 2006 , and in revised form, September 26, 2006.

^* This work was funded by grants from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council. 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. Tel.: 780-492-6485; Fax: 780-492-0450; E-mail: tom.hobman{at}ualberta.ca.

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

This article has been cited by other articles:

				N. S. Lee, D. H. Kim, J. Alluin, M. Robbins, S. Gu, H. Li, J. Kim, P. M. Salvaterra, and J. J. Rossi Functional and intracellular localization properties of U6 promoter-expressed siRNAs, shRNAs, and chimeric VA1 shRNAs in mammalian cells RNA, September 1, 2008; 14(9): 1823 - 1833. [Abstract] [Full Text] [PDF]

				K.-F. Tang, H. Ren, J. Cao, G.-L. Zeng, J. Xie, M. Chen, L. Wang, and C.-X. He Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB J. Cell Biol., July 28, 2008; 182(2): 233 - 239. [Abstract] [Full Text] [PDF]