Identification of a novel promyelocytic leukemia zinc-finger isoform required for colorectal cancer cell growth and survival.

Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor that regulates proliferation, differentiation and apoptosis among various cellular origins. PLZF expression is upregulated in colorectal cancer cell lines but its putative functional role in this context is unknown. Here, we report the identification of a novel p65 PLZF isoform that results from the usage of an evolutionarily conserved alternative translational initiation site. This isoform is devoid of the classical BTB/POZ domain required for nuclear localization and transcriptional repression. Depletion of p65 PLZF expression in colorectal cancer cell lines results in reduction of cell growth, loss of cell anchorage and increase in cell apoptosis. Overall, these results indicate that p65 PLZF is crucial to maintain colorectal cancer cell adhesion as well as survival and must occur independently of the traditionally viewed transcriptional role of PLZF in the course of these biological processes.