 Peter
Howley, M.D., is the Shattuck Professor of Pathological Anatomy
Chairman
of the Department of Pathology at Harvard
Medical School. Research in the Howley
laboratory
is focused on the molecular biology of
cancer and the role of viruses in its
formation.
The lab studies "high risk" HPV
types such as HPV16 and HPV18 encode two
oncoproteins, E6 and E7, which target the
important cellular growth regulatory proteins
p53 and pRb, respectively. They have previously
shown that E6 promotes the ubiquitination
and degradation of p53, and are now interested
in the general question of how proteins
are recognized within cell by the ubiquitin
proteolytic machinery. The E6 promoted
ubiquitylation
of p53 is mediated by a cellular protein,
, called the E6 Associated Protein (E6AP),
that binds to E6 and participates directly
in its ubiquitination. We are interested
in how E6AP is regulated and the identification
of additional cellular proteins that E6AP
targets in cells, either in the presence
of or absence of the viral E6 protein.
Selected Publications:
Walters, K.J., Lech, P.J., Goh, A.M.
Wang, Q., and Howley, P.M. (2003)
Binding of the proteasomal subunit
S5a opens the quartenary structure
of the DNA repair protein hHR23a.
Proc. Nat. Acad. Sci.
USA 100:12694-12699
Kleijnen, M.F., Alarcón, R.M.
and Howley, P.M. (2003) The ubiquitin-associated
(uba) domain of PLIC-2 interacts with
the proteasome. Mol. Biol.
Cell, 14:3868-3875.
You, J. Croyle, J.L., Nishimura, A.,
Ozato, K., and Howley, P.M. (2004)
Interaction of the bovine papillomavirus
E2 protein with Brd4 tethers the viral
DNA to host mitotic chromosomes. Cell,
117:349-360. |
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