Role of the β isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation

Abstract

The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the β isoform of the 14-3-3 proteins (14-3-3β) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Over-expression of 14-3-3 β in NIH 3T3 cells stimulated cell growth and supported anchorage-independent growth in soft agar medium and tumor formation in nude mice. To elucidate the molecular mechanisms of 14-3-3 β-mediated NIH 3T3 transformation, we examined the activity of mitogen-activated protein kinase (MAPK) after serum stimulation. Overexpression of 14-3-3 β augmented MAPK activity after serum stimulation, and MAPK activity correlated well with the amount of 14-3-3 β expression. The colony-forming ability of NIH 3T3 cells over-expressing 14-3-3 β in soft agar medium was efficiently abolished by exogenous expression of a dominant-negative mutant of MEK1 and 14-3-3 β physically interacted with Raf-1 in these cells. These findings indicate that 14-3-3 β has oncogenic potential, mainly through enhancement of Raf-1 activation and resultant augmentation of signaling in the MAPK cascade.