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Cell
Cycle Regulation and Cardiovascular Biology
Efforts toward cellular regeneration of damaged myocardium have been limited
by the inability of cardiac myocytes to undergo mitosis. While mitotic
entry requires the coordinated expression of many genes, little is known
about how this is regulated at the level of transcription. Our laboratory's
goal is to understand the transcriptional regulation of cell division,
and how such processes play a role in cardiovascular biology and disease.
We recently cloned human Cdc5 during a screen for novel signaling elements
involved in cell division. We subsequently have shown that it is a positive
transcriptional regulator of G2/M. Homology with expressed sequences in
lower eukaryotes demonstrates that it is a member of a protein family
that has been conserved through evolution. Aside from its role in G2/M,
however, little else is known about how Cdc5 functions. One of the current
focuses in our lab is to identify the mechanisms by which Cdc5 is regulated,
and the targets that mediate its effects on G2/M. This work involves the
study of phosphorylation and nuclear translocation events, as well as
the interrogation of DNA-protein binding interactions. Another avenue
of inquiry is the use of high-throughput screening methods to identify
other gene products that regulate the behavior of non-dividing cells.
To provide a model system for investigating the mechanisms by which cells
lose the ability to divide, we are developing myocyte culture and transfection
methods that will allow us to manipulate the proliferation program in
these post-mitotic cells.
Selected Publications:
Bernstein, H.S. and Coughlin, S.R. (1997) Pombe Cdc5-related protein:
A putative human transcription factor implicated in mitogen-activated
signaling. J Biol Chem 272(9):5833-5837.
Bernstein, H.S. and Coughlin, S.R. (1998) A mammalian homolog of fission
yeast Cdc5 regulates G2 progression and mitotic entry. J Biol Chem 273(8):4666-4671.
Lei, X.-H., Shen, X., Xu, X.-Q. and Bernstein, H.S. (1999) Cdc5 acts as
a site-specific DNA binding protein in higher eukaryotes. In review.
Contact Information:
Email: hsbernstein @pedcard.ucsf.edu
Phone: 415/ 502-8633
Address: Box 0130, Room M 1336
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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