PIM1
PIM1 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Overview
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.
CIViC holds 5 clinical evidence items and 0 assertions across 5 variants, naming Ibrutinib. Open Targets scores its association with cancer at 0.70 (direct and indirect evidence; datatypes literature 0.99, genetic association 0.48, somatic mutation 0.83, clinical 0.12). IntOGen calls it a driver in 6 cohorts (3 activating, 3 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Non-Hodgkin Lymphoma, Plasma Cell Myeloma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PIM1 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 1 · What it is
PIM1 is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 2 · What goes wrong in cancer
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis.
- 3 · How drugs use it
No product in this corpus aims at PIM1 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:8986 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P11309 (protein name, function text, keywords and locations (REST API)); CIViC gene PIM1 (5 evidence items, 0 assertions, 5 variants; diseases: Diffuse Large B-cell Lymphoma Activated B-cell Type, Lung Non-small Cell Carcinoma, Diffuse Large B-cell Lymphoma (GraphQL API, CC0)); Open Targets ENSG00000137193 (association with cancer (MONDO_0004992) 0.70; per-cancer scores at or above 0.5: diffuse large B-cell lymphoma 0.65, non-Hodgkin lymphoma 0.67 (GraphQL API, CC0)); IntOGen PIM1 (driver in 6 cohorts (Act 3, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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 stabilisation of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signalling 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. Location: Cytoplasm; Nucleus; Cell membrane (UniProt). Locus 6p21.2 (HGNC).
- Non-Hodgkin lymphoma: Open Targets association 0.67 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 1 cohort (NHL)
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
- Diffuse large B-cell lymphoma: Open Targets association 0.65 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease
- Non-small-cell lung cancer: CIViC evidence names this disease
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.12; IntOGen calls it an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 5 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Diffuse Large B-cell Lymphoma Activated B-cell Type.
Latest papers
topQuery for this target: (TITLE:"PIM1" OR ABSTRACT:"PIM1" OR TITLE:"Pim-1 proto-oncogene, serine/threonine kinase" OR ABSTRACT:"Pim-1 proto-oncogene, serine/threonine kinase" OR TITLE:"Serine/threonine-protein kinase pim-1" OR ABSTRACT:"Serine/threonine-protein kinase pim-1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PIM1, not a curated reading list.