PIM1

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. It plays a role in signal transduction in blood cells, contributing to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Both the human and orthologous mouse genes have been reported to encode two isoforms (with preferential cellular localization) resulting from the use of alternative in-frame translation initiation codons, the upstream non-AUG (CUG) and downstream AUG codons.

Pim-1 proto-oncogene, serine/threonine kinase

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, another 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. Promotes 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. Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (PubMed:18056989).
Promotes brown adipocyte differentiation (By similarity).

Apoptotic processIEA:UniProtKB-KW
Cell cycleIEA:UniProtKB-KW
Cellular detoxificationManual Assertion Based On ExperimentIMP:UniProtKB
Multicellular organism developmentManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of brown fat cell differentiationISS:UniProtKB
Positive regulation of cardiac muscle cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cardioblast proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cyclin-dependent protein serine/threonine kinase activityIDA:UniProtKB
Positive regulation of protein serine/threonine kinase activityIMP:UniProtKB
Positive regulation of transcription, DNA-templatedIEA:Ensembl
Protein autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilizationIEA:Ensembl
Regulation of hematopoietic stem cell proliferationIEA:Ensembl
Regulation of transmembrane transporter activityManual Assertion Based On ExperimentIMP:UniProtKB
Vitamin D receptor signaling pathwayManual Assertion Based On ExperimentIMP:CACAO

Isoform 1
Cytoplasm
Nucleus
Isoform 2
Cell membrane

Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation.
Ubiquitinated, leading to proteasomal degradation.