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Molecular and Cellular Biology, November 2008, p. 6858-6869, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00367-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Autophosphorylation-Induced Degradation of the Pho85 Cyclin Pcl5 Is Essential for Response to Amino Acid Limitation{triangledown}

Sharon Aviram,1,{dagger} Einav Simon,1 Tsvia Gildor,1 Fabian Glaser,2 and Daniel Kornitzer1*

Department of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion-I.I.T. and the Rappaport Institute for Research in the Medical Sciences, Haifa 31096, Israel,1 Bioinformatics Knowledge Unit, The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering, Technion-I.I.T., Haifa 32000, Israel2

Received 4 March 2008/ Returned for modification 18 April 2008/ Accepted 15 August 2008

Pho85 cyclins (Pcls), activators of the yeast cyclin-dependent kinase (CDK) Pho85, belong together with the p35 activator of mammalian CDK5 to a distinct structural cyclin class. Different Pcls target Pho85 to distinct substrates. Pcl5 targets Pho85 specifically to Gcn4, a yeast transcription factor involved in the response to amino acid starvation, eventually causing the degradation of Gcn4. Pcl5 is itself highly unstable, an instability that was postulated to be important for regulation of Gcn4 degradation. We used hybrids between different Pcls to circumscribe the substrate recognition function to the core cyclin box domain of Pcl5. Furthermore, the cyclin hybrids revealed that Pcl5 degradation is uniquely dependent on two distinct degradation signals: one N-terminal and one C-terminal to the cyclin box domain. Whereas the C-terminal degradation signal is independent of Pho85, the N-terminal degradation signal requires phosphorylation of a specific threonine residue by the Pho85 molecule bound to the cyclin. This latter mode of degradation depends on the SCF ubiquitin ligase. Degradation of Pcl5 after self-catalyzed phosphorylation ensures that activity of the Pho85/Pcl5 complex is self-limiting in vivo. We demonstrate the importance of this mechanism for the regulation of Gcn4 degradation and for cell growth under conditions of amino acid starvation.

* Corresponding author. Mailing address: Department of Molecular Microbiology, B. Rappaport Faculty of Medicine, 2 Efron St., Haifa 31096, Israel. Phone: 972-4-829 5258. Fax: 972-4-829 5254. E-mail: danielk{at}techunix.technion.ac.il

{triangledown} Published ahead of print on 15 September 2008.

{dagger} Present address: University of Texas Southwestern Medical Center, Dallas, TX 75390-9185.

Molecular and Cellular Biology, November 2008, p. 6858-6869, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.00367-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Streckfuss-Bomeke, K., Schulze, F., Herzog, B., Scholz, E., Braus, G. H. (2009). Degradation of Saccharomyces cerevisiae Transcription Factor Gcn4 Requires a C-Terminal Nuclear Localization Signal in the Cyclin Pcl5. Eukaryot Cell 8: 496-510 [Abstract] [Full Text]  


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