Martha Cyert
Academic Appointments
- Professor, Biology (School of Humanities and Sciences)
- Member, Bio-X
Key Documents
Contact Information
- Academic Offices
Personal Information Email Tel (650) 723-9970
Professional Overview
Administrative Appointments
- Senior Associate Vice Provost for Undergraduate Education, Stanfiord University (2010 - present)
Honors and Awards
- Thomas W. and Susan B. Ford University Fellow in Undergraduate Education, Stanford University (2012-present)
- Terman Fellow, Stanford University (2000)
- Scholar, Lucille P. Markey Charitable Trust (1997)
Professional Education
| Postdoctoral Fellow: | University of California, Berkeley, Biochemistry (1992) |
| A.B.: | Harvard University, Biochemistry (1980) |
| Ph D.: | UCSF, Genetics (1988) |
Graduate & Fellowship Program Affiliations
Internet Links
Scientific Focus
Current Research Interests
The Cyert lab studies Ca2+- dependent signal transduction mediated by calcineurin, the highly conserved Ca2+/calmodulin-regulated protein phosphatase. Calcineurin, which is specifically inhibited by the immunosuppressant drugs FK506 and cyclosporin A, regulates many Ca2+-dependent processes in mammalian cells, including T-cell activation, heart valve development, cardiac hypertrophy and some aspects of learning and memory. In several pathogenic fungi, calcineurin is required for virulence. In bakers yeast, Saccharomyces cerevisiae, calcineurin promotes cell survival during environmental stress (Cyert(2003) BBRC). Research in the lab has three major goals: 1) To identify, comprehensively, calcineurin substrates and regulators in yeast, 2) to elucidate the function of each of these proteins and understand how calcineurin regulates its activity, and 3) to define conserved aspects of substrate recognition and dephosphorylation by calcineurin, using this collection of substrates. Current studies employ proteomic approaches, including protein microarrays and mass spectrometry, to achieve the complete identification of calcineurin substrates. Several substrates have already been identified, and studies of these substrates demonstrate the wide variety of cellular processes that are regulated by calcineurin. For example, calcineurin activates Ca2+-dependent gene expression by dephosphorylating the Crz1 transcription factor and causing its translocation to the nucleus (Cyert (2003) BBRC). Other calcineurin substrates include Slm1 and Slm2, which are required for endocytosis (Bultynck et al 2006), and Aly1, which regulates the yeast response to nutrients and modulates intracellular trafficking of a critical amino acid permease, Gap1. Aly1 is a member of the alpha-arrestin family; these proteins are related to alpha-arrestins, which regulate the signaling and trafficking of G-protein coupled receptors in vertebrates. Calcineurin also dephosphorylates Hph1, an integral ER protein that interacts the Sec63 complex, which is required for post-translational protein translocation into the ER (Heath et al 2004). Calcineurin positively regulates Hph1, suggesting that it promotes Sec63-dependent translocation of membrane proteins into the ER increases during environmental stress. Future studies will investigate how these different calcineurin-dependent dephosphorylation events are coordinated in vivo. Calcineurin interacts with at least two distinct structural motifs in its substrates. Each of the yeast substrates contains a conserved sequence, termed the PxIxIT motif, which determines its affinity for calcineurin (Roy et al. 2007). Furthermore, changing the affinity of the PxIxIT motif in Crz1 for calcineurin changes the Ca2+ concentration dependence of Crz1-dependent gene in vivo. Calcineurin also recognizes a second motif in substrates, LxVP (Rodriguez et al 2009). LxVP binding to active calcineurin is required for substrate dephosphorylation, and the immunosuppressants, FK506 and cyclosporin A, apparently inhibit calcineurin by preventing this interaction.
Publications
- Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation. Eukaryot Cell. 2011; (11): 1574-81
- Hph1 and Hph2 are novel components of the Sec63/Sec62 posttranslational translocation complex that aid in vacuolar proton ATPase biogenesis. Eukaryot Cell. 2011; (1): 63-71
- Alpha-arrestins Aly1 and Aly2 regulate intracellular trafficking in response to nutrient signaling. Mol Biol Cell. 2010; (20): 3552-66
- A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants. Mol Cell. 2009; (5): 616-26
- Cracking the phosphatase code: docking interactions determine substrate specificity. Sci Signal. 2009; (100): re9
- A conserved docking site modulates substrate affinity for calcineurin, signaling output, and in vivo function. Mol Cell. 2007; (6): 889-901
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