Gene expression data from hCdc73 knock-down HEK293 cells under confluent and sparse condition.

The parafibromin/hCdc73 is a component of the PAFc, which controls RNA polymerase II-mediated general transcription. In parathyroid carcinoma and familial autosomal dominant hyperparathyroidism-jaw tumor (HPT-JT), hCdc73 mutations are heavily implicated, yet the underlying mechanism of its carcinogenic action is poorly understood. Here, we demonstrate that hCdc73 specifically controls mRNA stability of p53, and p53-mediated apoptosis. hCdc73 is associated with mature p53 mRNA in the cytoplasm and facilitates its degradation. Cytoplasmic hCdc73 physically interacts with eEF1Bγ and hSki8, and this interaction is required to bind and destabilize p53 mRNA. Furthermore, enhanced association of p53 mRNA with a cancer driven hCdc73(K34Q) mutant was also observed. As a result, reduced p53 expression as well as enhanced cell proliferation was acquired in the hCdc73 (K34Q) overexpressed cells. Altogether, our findings indicate that hCdc73 directly targets p53 mRNA to repress p53 expression, and aberrant regulation of this interaction may lead to tumor progression. Total RNA was obtained from control siRNA or hCdc73 siRNA transfected cells, under sparse or confluent cell density condition.