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Genes Dev. 2003 Aug 1;17(15):1841-54. Epub 2003 Jul 17.

The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor.

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1
Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.

Abstract

Growth factor withdrawal results in the termination of factor-dependent transcription. One transcript that declines rapidly following growth factor deprivation of hematopoietic cells is the serine/threonine kinase pim-2. When constitutively expressed, Pim-2 conferred long-term resistance to a variety of apoptotic stimuli including growth factor withdrawal and endogenous levels of Pim-2 contributed to growth factor-mediated apoptotic resistance. Pim-2 expression maintained cell size and mitochondrial potential independently of the PI3K/Akt/TOR pathway. Pim-2-dependent maintenance of cell size and survival correlated with its ability to maintain rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 and phosphorylation of the BH3 protein BAD. These results establish Pim-2 as a direct link between growth factor-induced transcription and a novel, kinase-dependent pathway that promotes cell-autonomous survival.

PMID:
12869584
PMCID:
PMC196230
DOI:
10.1101/gad.1105003
[Indexed for MEDLINE]
Free PMC Article
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