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Genes Cells

Title:		Sequence elements that contribute to the degradation of yeast G alpha
Author(s):		Schauber C; Chen L; Tongaonkar P; Vega I; Madura K;
Address:		"Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA"
Journal Title:		Genes Cells
Year:		1998
Volume:		3
Issue:		5
Page Number:		307 - 319
DOI:		10.1046/j.1365-2443.1998.00192.x
ISSN/ISBN:		1356-9597 (Print) 1356-9597 (Linking)
Abstract:		"BACKGROUND: Gpa1 is the alpha subunit of the yeast G-protein that regulates signal transduction during mating. The stability of Galpha/Gpa1 is influenced by the ubiquitin-dependent N-end rule pathway, suggesting that the regulation of G alpha levels may be important for effective mating response and recovery. RESULTS: The G alpha sequences that confer sensitivity to degradation by the N-end rule pathway were identified. The insertion of this degradation signal (G1-Deg) into the ordinarily stable Gpa2 protein conferred proteolytic targeting. We examined G alpha degradation under different conditions and found that it was efficiently degraded in haploid and diploid cells, but was stable if it was synthesized prior to expression of the N-end rule pathway. Interestingly, a specific mutation in G alpha that is believed to promote the GTP-bound form (N388K) caused accelerated degradation. CONCLUSION: A region encompassing a putative effector-binding domain (G1-Deg) is required for G alpha degradation via the N-end rule pathway. Our studies have shown that G alpha is susceptible to proteolysis soon after synthesis. These results are in agreement with the idea that G alpha is more unstable in the GTP-bound form, which is the predominant state of monomeric/free G alpha soon after synthesis. It is likely that the signal transduced by Gbetagamma can be regulated by adjusting the levels of G alpha through proteolysis"
Keywords:		"Amino Acid Sequence Diploidy Enzyme Stability Fungal Proteins/metabolism *GTP-Binding Protein alpha Subunits GTP-Binding Protein alpha Subunits, Gq-G11 GTP-Binding Proteins/chemistry/genetics/*metabolism *GTPase-Activating Proteins Haploidy *Heterotrimeri;"
Notes:		"MedlineSchauber, C Chen, L Tongaonkar, P Vega, I Madura, K eng GM52058/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. England 1998/07/31 Genes Cells. 1998 May; 3(5):307-19. doi: 10.1046/j.1365-2443.1998.00192.x"