The Role of Gabp-a/b in the Proliferation of Nih-3t3 Cells: One Search of an Expected Function, Leading to Rather Unexpected Finds

GABP is a heterodymeric Ets-family transcription factor with over 60 potential target genes. Many of them are involved directly or indirectly in the regulation of sell proliferation. Their function though, can be extremely diverse. This work sheds light on one of the least investigated connections between GABP and the cell proliferation - the apoptosis. Connection, which up to now remained largely obscure. Overexpression of GABP in NIH-3T3 cells is inducing not strong, but only dampened apoptotic processes via prominent activation of caspase-12. Interestingly, activation of downstream effector caspases is suppressed, leading the cell culture to a stable, so-called "pre-apoptotic" status characterized with decreased proliferation speed. Caspase-12 activation though, is not due to ER Overload Response, which suggests that it may reflect the normal physiological mechanism of caspase-12 regulation.