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

J. Biol. Chem., Vol. 278, Issue 49, 48727-48734, December 5, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/49/48727    most recent M308671200v1 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 Kaplun, L. Articles by Raveh, D. Search for Related Content PubMed PubMed Citation Articles by Kaplun, L. Articles by Raveh, D. Social Bookmarking                      What's this?

DNA Damage Response-mediated Degradation of Ho Endonuclease via the Ubiquitin System Involves Its Nuclear Export^*

Ludmila Kaplun, Yelena Ivantsiv, Anna Bakhrat, and Dina Raveh

From the Department of Life Sciences, Ben Gurion University of the Negev, Beersheba, Israel 84105

Yeast mating switch Ho endonuclease is rapidly degraded by the ubiquitin system and this depends on the DNA damage response functions, MEC1, RAD9, and CHK1. A PEST sequence marks Ho for degradation. Here we show that the novel F-box receptor, Ufo1, recruits phosphorylated Ho for degradation. Mutation of PEST residue threonine 225 stabilizes Ho, yet HoT225A still binds Ufo1 in vitro. Stable HoT225A accumulates within the nucleus, whereas HoT225E is degraded. Deletion of the nuclear exportin Msn5 traps native Ho in the nucleus and extends its half-life. These experiments suggest that Ho is degraded in the cytoplasm. In mec1 mutants stable Ho accumulates within the nucleus; Ho produced in mec1 cells does not bind Ufo1. Thus the MEC1 pathway has functions both in phosphorylation of Thr-225 for nuclear export and in additional phosphorylations for binding Ufo1. Cells with HO under its genomic promoter, but stabilized by deletion of the Msn5 exportin, proliferate, but are multibudded. These experiments elucidate some of the links between the DNA damage response and degradation of Ho by the ubiquitin system.

Received for publication, August 6, 2003 , and in revised form, September 12, 2003.

^* This work was supported by the Association for International Cancer Research, the German Israel Scientific Research Foundation, and the Israel Cancer Association. 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.

All authors contributed equally to the work.

To whom correspondence should be addressed. Tel.: 972-8-646-1371; Fax: 972-8-647-9190; E-mail: raveh{at}bgumail.bgu.ac.il.

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

This article has been cited by other articles:

				J. Towpik, D. Graczyk, A. Gajda, O. Lefebvre, and M. Boguta Derepression of RNA Polymerase III Transcription by Phosphorylation and Nuclear Export of Its Negative Regulator, Maf1 J. Biol. Chem., June 20, 2008; 283(25): 17168 - 17174. [Abstract] [Full Text] [PDF]

				B. Ding, C.-j. Liu, Y. Huang, J. Yu, W. Kong, and P. Lengyel p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins J. Biol. Chem., May 26, 2006; 281(21): 14893 - 14906. [Abstract] [Full Text] [PDF]

				A. Bakhrat, K. Baranes, O. Krichevsky, I. Rom, G. Schlenstedt, S. Pietrokovski, and D. Raveh Nuclear Import of Ho Endonuclease Utilizes Two Nuclear Localization Signals and Four Importins of the Ribosomal Import System J. Biol. Chem., May 5, 2006; 281(18): 12218 - 12226. [Abstract] [Full Text] [PDF]

				Y. Ivantsiv, L. Kaplun, R. Tzirkin-Goldin, N. Shabek, and D. Raveh Unique Role for the UbL-UbA Protein Ddi1 in Turnover of SCFUfo1 Complexes. Mol. Cell. Biol., March 1, 2006; 26(5): 1579 - 1588. [Abstract] [Full Text] [PDF]

				L. Kaplun, R. Tzirkin, A. Bakhrat, N. Shabek, Y. Ivantsiv, and D. Raveh The DNA Damage-Inducible UbL-UbA Protein Ddi1 Participates in Mec1-Mediated Degradation of Ho Endonuclease Mol. Cell. Biol., July 1, 2005; 25(13): 5355 - 5362. [Abstract] [Full Text] [PDF]

				S. Bose, J. A. Dutko, and R. S. Zitomer Genetic Factors That Regulate the Attenuation of the General Stress Response of Yeast Genetics, March 1, 2005; 169(3): 1215 - 1226. [Abstract] [Full Text] [PDF]

				N. Spielewoy, K. Flick, T. I. Kalashnikova, J. R. Walker, and C. Wittenberg Regulation and Recognition of SCFGrr1 Targets in the Glucose and Amino Acid Signaling Pathways Mol. Cell. Biol., October 15, 2004; 24(20): 8994 - 9005. [Abstract] [Full Text] [PDF]

				S. Smith, J.-Y. Hwang, S. Banerjee, A. Majeed, A. Gupta, and K. Myung Mutator genes for suppression of gross chromosomal rearrangements identified by a genome-wide screening in Saccharomyces cerevisiae PNAS, June 15, 2004; 101(24): 9039 - 9044. [Abstract] [Full Text] [PDF]

				A. Bakhrat, M. S. Jurica, B. L. Stoddard, and D. Raveh Homology Modeling and Mutational Analysis of Ho Endonuclease of Yeast Genetics, February 1, 2004; 166(2): 721 - 728. [Abstract] [Full Text] [PDF]