William Tansey
Professor
Ph.D., University of Sydney, 1991
Oncogene regulation; transcription; protein destruction
email tansey@cshl.edu,
phone (516) 367-8436, fax (516) 367-8874
Transcription and ubiquitin-mediated proteolysis are two processes that
might seem to have little in common. Transcription is the first step in
the life of any protein; proteolysis the last. Despite the disparate nature
of these processes, a growing body of evidence suggests that components
of the ubiquitin–proteasome system are intimately involved in the
regulation of gene expression. Research in our laboratory is geared toward
understanding how these two processes intersect, and the consequences
of this intersection for cellular growth control.
Our current research is divided into two areas. One area is focused on
revealing the basic mechanisms that connect the transcription and ubiquitin
systems. We have previously found that the destruction of transcription
factors is intimately tied to their ability to activate transcription,
and that components of the proteasome play an essential role in the regulation
of histone modifications. We are currently studying how prototypical transcription
factors, such as the yeast activator Gal4, interact with ubiquitin and
with the proteasome to regulate gene expression.
Our second area of research is focused on understanding how the destruction
of transcription factors impacts mammalian cell growth control. These
studies center on Myc, an oncoprotein transcription factor that features
prominently in human cancer. We have previously found that Myc is rapidly
destroyed by the ubiquitin-system, and that oncogenic mutations within
Myc stabilize the protein, allowing it to accumulate. We seek to identify
the cellular machinery that targets Myc for ubiquitin-mediated destruction,
and learn how the regulation of Myc turnover—and loss of control
of this process—relates to human cancer.
Please visit the Tansey
Lab home page.
Selected Publications
Lee, D., Ezhkova, E., Li, B., Pattenden, S.G., Tansey, W.P., and Workman,
J.L. 2005. The proteasome regulatory particle alters the SAGA coactivator
to ehance its interactions with transcriptional coactivators. Cell
123: 423–436.
Muratani, M., Kung, C., Shokat, K.M., and Tansey, W.P. 2005. The F-box
protein Dsg1/Mdm30 is a transcriptional co-activator that stimulates Gal4
turnover and cotranscriptional mRNA processing. Cell 120:
887–899.
Herbst, A., Hemann, M.T., Tworkowski, K.A., Salghetti, S.E., Lowe, S.W.,
and Tansey, W.P. 2005. A conserved element in Myc that negatively regulates
its pro-apoptotic activity. EMBO Rep. 6: 177–183.
Ezhkova, E., and Tansey, W.P. 2004. Proteasomal ATPases
link ubiquitylation of histone H2B to methylation of histone H3. Mol.
Cell 13: 435–442.
Kim, S.-Y., Herbst, A., Twokowski, K.A., Salghetti,
S.E., and Tansey, W.P. 2003. Skp2 regulates Myc protein stability and
activity. Mol. Cell 11: 1177–1188.
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