Abstract:
The cell-cycle checkpoint protein p53 both directs terminal differentiation and protects embryos
from DNA damage. To study invertebrate p53 during early development, we identified three differentially
expressed p53 family members (p53, p97, p120) in the surf clam, Spisula solidissima.
In these mollusks, p53 and p97 occur in both embryonic and adult tissue, whereas p120 is exclusively
embryonic. We sequenced, cloned, and characterized p120 cDNA. The predicted protein,
p120, resembles p53 across all evolutionarily conserved regions and contains a C-terminal extension
with a sterile alpha motif (SAM) as in p63 and p73. These vertebrate forms of p53 are
required for normal inflammatory, epithelial, and neuronal development. Unlike clam p53 and
p97, p120 mRNA and protein levels are temporally expressed in embryos, with mRNA levels
decreasing with increasing p120 protein (R2 = 0.97). Highest surf clam p120 mRNA levels coincide
with the onset of neuronal growth. In earlier work we have shown that neuronal development
is altered by exposure to polychlorinated biphenyls (PCBs), a neurotoxic environmental
contaminant. In this study we show that PCBs differentially affect expression of the three surf
clam p53 family members. p120 mRNA and protein are reduced the most and earliest in development,
p97 protein shows a smaller and later reduction, and p53 protein levels do not change. For
the first time we report that unlike p53 and p97, p120 is specifically embryonic and expressed in
a time-dependent manner. Furthermore, p120 responds to PCBs by 48 hr when PCB-induced
suppression of the serotonergic nervous system occurs.
