Piers Nash

Signal Transduction Reversible ubiquitination and regulation of signaling: Protein ubiquitination can have many outcomes depending on the length of the ubiquitin chain and the type of linkage. The 2004 Nobel Prize in Chemistry was awarded for the elucidation of the ubiutin-proteasome pathway in which proteins tagged with Lys-48-linked ubiquitin chains greater than 3 in length (polyubiquitination) are targeted to the proteasome for degradation. By contrast, short chains of Lys-63-linked ubiquitin act to coordinate the endocytic machinery and the internal trafficking of endocytic vesicles. We are interested ubiquitination as a regulated and reversible process that creates docking sites for a range of ubiquitin-binding proteins. We are currently studying the role of various ubiqutin linkages in regulating signaling events from activated cell surface receptors (the EGF-R and the T-cell receptor), and the role of specific deubiquitinating enzymes in modulating cellular signal transduction.

Signal Transduction Reversible ubiquitination and regulation of signaling: Protein ubiquitination can have many outcomes depending on the length of the ubiquitin chain and the type of linkage. The 2004 Nobel Prize in Chemistry was awarded for the elucidation of the ubiutin-proteasome pathway in which proteins tagged with Lys-48-linked ubiquitin chains greater than 3 in length (polyubiquitination) are targeted to the proteasome for degradation. By contrast, short chains of Lys-63-linked ubiquitin act to coordinate the endocytic machinery and the internal trafficking of endocytic vesicles. We are interested ubiquitination as a regulated and reversible process that creates docking sites for a range of ubiquitin-binding proteins. We are currently studying the role of various ubiqutin linkages in regulating signaling events from activated cell surface receptors (the EGF-R and the T-cell receptor), and the role of specific deubiquitinating enzymes in modulating cellular signal transduction.

iu, B.A., Jablonowski, K., Raina, M., Arcé, M., Pawson, T., and Nash, P.D. (2006) The Human and Mouse Complement of SH2 Domain Proteins – establishing the boundaries of phosphotyrosine signaling. Molecular Cell 22: 851-868. 

Nash, P., Tang, X., Orlicky, S., Chen, Q., Gertler, F.B., Mendenhall, M.D., Sicheri, F., Pawson, T., Tyers, M. (2001) Multi-site phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature 414: 514-521 

Nash, P., Berry, D., Liu, S., Pawon, T., McGlade, J. (2002). A high affinity Arg-X-X-Lys SH3-binding motif confers specificity for the interaction between Gads and SLP-76 in T-cell signaling. Current Biology 12: 1336-1341. 

Liu, Q., Nash, P., Berry, D., Pawson, T., McGlade, J., Li, S. (2003) Structural Basis for Specific Binding of the Gads SH3 domain to an RXXK Motif-containing Slp-76 Peptide: A Novel Mode of Peptide Recognition. Molecular Cell 11: 471-481. 

iu, B.A., Jablonowski, K., Raina, M., Arcé, M., Pawson, T., and Nash, P.D. (2006) The Human and Mouse Complement of SH2 Domain Proteins – establishing the boundaries of phosphotyrosine signaling. Molecular Cell 22: 851-868. 

Nash, P., Tang, X., Orlicky, S., Chen, Q., Gertler, F.B., Mendenhall, M.D., Sicheri, F., Pawson, T., Tyers, M. (2001) Multi-site phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature 414: 514-521 

Nash, P., Berry, D., Liu, S., Pawon, T., McGlade, J. (2002). A high affinity Arg-X-X-Lys SH3-binding motif confers specificity for the interaction between Gads and SLP-76 in T-cell signaling. Current Biology 12: 1336-1341. 

Liu, Q., Nash, P., Berry, D., Pawson, T., McGlade, J., Li, S. (2003) Structural Basis for Specific Binding of the Gads SH3 domain to an RXXK Motif-containing Slp-76 Peptide: A Novel Mode of Peptide Recognition. Molecular Cell 11: 471-481.