Why p53 micro-injection of monoclonal
antibodies induces a growth arrest ?
The carboxy-terminus of Hp53 has been
shown to play an important role in
controlling the specific DNA binding
function. Wils type p53 is found in a latent
form whicvh does not bind to DNA. The
specific DNA binding activity was shown to
be activated by various pathways:
phosphorylation (Hupp et al., 1992), antibody
specific for the carboxy-terminus of the
protein (Hupp et al., 1992), small peptides
which could mimic the carboxy-terminus of
the p53 (Hupp et al., 1995), short single
stranded DNA (Jayaraman & Prives, 1995),
deletion of the last 30 amino-acids (Hupp et
al., 1992) and the interaction with a cellular
protein (Jayaraman et al., 1997).
This observation suggest that micro-
injection of antibodies such as PAb421
induces an activation of the transcriptional
activity of p53. Such hypothesis have been
confirmed (Hupp et al., 1995)