|
p53 is the most frequently mutated tumor suppressor gene in human cancer. It is a
transcription factor that responds to diverse intracellular and extracellular stress signals.
Depending on the level of stress encountered, p53 will induce cell cycle arrest, DNA repair, or
apoptosis by transactivating or transrepressing target genes that mediate these responses.
p53 is a critical nodal point in the response to a variety of cellular stress, and its
inactivation constitutes one of the major transition points in the development of cancer.
Unlike other tumor suppressor genes whose expression is lost during the carcinogenesis process,
the mutant p53 protein is overexpressed, and its expression is associated with genomic
instability and chemotherapy resistance. The vast majority (74%) of p53 mutations are a
single base change (missense) in its core DNA binding domain that results in the production of
a full-length protein generally lacking wild-type functions. Epidemiological, cellular
and animal studies strongly suggest that mutant p53 (mtp53) can act as an oncogene.
My lab is interested in determining the underlying mechanism(s) for mtp53’s oncogenic activity.
We use a variety of approaches to address this question including examining gene expression
changes induced by mtp53, identifying mtp53-interacting proteins, and dissecting mtp53’s
ability to regulate gene expression at the promoter level. The long-term aim of the lab
is to elucidate the critical functions mutant p53 utilizes to promote cancer development, in
order to generate new targets for therapeutic intervention. |
