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

J. Biol. Chem., Vol. 277, Issue 27, 23981-23984, July 5, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/27/23981    most recent C200203200v1 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 Yonkovich, J. Articles by Zhu, Z. Search for Related Content PubMed PubMed Citation Articles by Yonkovich, J. Articles by Zhu, Z.

ACCELERATED PUBLICATION
Copper Ion-sensing Transcription Factor Mac1p Post-translationally Controls the Degradation of Its Target Gene Product Ctr1p^*

Jesse Yonkovich, Roslyn McKenndry, Xiaoli Shi, and Zhiwu Zhu

From the Department of Environmental Toxicology, University of California, Santa Cruz, California 95064

Copper ion uptake must be regulated to avoid both deficiency and excess because its essential yet toxic biological nature depends on the concentration. Yeast copper uptake is controlled at both the transcriptional and post-translational levels. The transcription of CTR1 and CTR3, encoding high affinity copper ion transporters, is regulated by the copper ion-sensing transcription factor Mac1p through the cis-acting copper ion-responsive elements in CTR1 and CTR3 promoters. Ctr1p is known to undergo degradation in cells exposed to high copper levels. We report that Mac1p is also required for copper-dependent Ctr1p degradation. Both mutations within a conserved copper ion binding motif, the "Cu-fist" in the Mac1p DNA-binding domain, and within a metal ion binding motif, REP-III located in the cytosolic domain of Ctr1p, cause defects in Ctr1p turnover. Furthermore, we show that the Mac1p limits intracellular copper accumulation likely by controlling Ctr1p degradation. The findings have uncovered an unprecedented mechanism by which a transcription factor not only regulates its target gene transcription but also controls the degradation of its target gene product.

This article has been cited by other articles:

				G. Keller, A. Bird, and D. R. Winge Independent Metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae Eukaryot. Cell, November 1, 2005; 4(11): 1863 - 1871. [Abstract] [Full Text] [PDF]

				J. C. Rutherford and A. J. Bird Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells Eukaryot. Cell, February 1, 2004; 3(1): 1 - 13. [Full Text] [PDF]

				G. D. Kruh Lustrous Insights into Cisplatin Accumulation: Copper Transporters Clin. Cancer Res., December 1, 2003; 9(16): 5807 - 5809. [Full Text] [PDF]

				X. Shi, K. Chabarek, A. Budai, and Z. Zhu Iron Requirement for GAL Gene Induction in the Yeast Saccharomyces cerevisiae J. Biol. Chem., October 31, 2003; 278(44): 43110 - 43113. [Abstract] [Full Text] [PDF]

				J. L. Nitiss A copper connection to the uptake of platinum anticancer drugs PNAS, October 29, 2002; 99(22): 13963 - 13965. [Full Text] [PDF]