PIM1, Serine/threonine-protein kinase pim-1
Enzyme Classification 18.104.22.168
Also Known as
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis. Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins (By similarity). Binds to RP9 (By similarity). Isoform 2, but not isoform 1, binds BMX (PubMed:16186805). Isoform 1 interacts with CDKN1B and FOXO3 (PubMed:18593906). Interacts with BAD (By similarity). Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM1, ubiquitination and proteasomal degradation (PubMed:12473674). Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteosomal degradation (PubMed:15798097). Interacts with CDKN1A (PubMed:12431783). Interacts with CDC25C (PubMed:16356754). Interacts (via N-terminal 96 residues) with CDC25A (By similarity). Interacts with MAP3K5 (PubMed:19749799). Interacts with MYC (By similarity). Interacts with CBX3 (PubMed:10664448).