PML
PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
Overview
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs.
CIViC holds 7 clinical evidence items and 0 assertions across 6 variants, naming Tretinoin, Arsenic Trioxide and Tamibarotene. Open Targets scores its association with cancer at 0.75 (direct and indirect evidence; datatypes literature 0.99, affected pathway 0.87, genetic association 0.63, somatic mutation 0.80). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Lung. In OnCo, 2 product records name it (Arsenic trioxide and Tretinoin (all-trans retinoic acid, ATRA)).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
- 1 · What it is
PML (PML nuclear body scaffold) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, a tumour suppressor, a biomarker and a fusion partner, and an approved or late-stage drug is recorded against it. Tied to Leukaemia, Thyroid cancer, Lung cancer and 3 more.
- 2 · What goes wrong in cancer
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms.
- 3 · How drugs use it
No product in this corpus aims at PML yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:9113 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P29590 (protein name, function text, keywords and locations (REST API)); CIViC gene PML (7 evidence items, 0 assertions, 6 variants; diseases: Acute Promyelocytic Leukaemia (GraphQL API, CC0)); Open Targets ENSG00000140464 (association with cancer (MONDO_0004992) 0.75; per-cancer scores at or above 0.5: thyroid cancer 0.57, skin cancer 0.53, myeloproliferative neoplasm 0.52, leukaemia 0.58 (GraphQL API, CC0)); IntOGen PML (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localisation and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. Location: Nucleus; Nucleus, nucleoplasm; Cytoplasm; Nucleus, PML body (UniProt). Locus 15q24.1 (HGNC).
- Leukaemia: Open Targets association 0.58 with leukaemia (MONDO_0005059)
- Thyroid cancer: Open Targets association 0.57 with thyroid cancer (MONDO_0002108)
- Lung cancer: IntOGen driver in 1 cohort (LUNG)
- Skin cancer: Open Targets association 0.53 with skin cancer (MONDO_0002898)
- Myeloproliferative neoplasms: Open Targets association 0.52 with myeloproliferative neoplasm (MONDO_0020076)
- Acute promyelocytic leukaemia: 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: CIViC lists 3 therapies; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 7 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"PML" OR ABSTRACT:"PML" OR TITLE:"PML nuclear body scaffold" OR ABSTRACT:"PML nuclear body scaffold" OR TITLE:"TRIM19" OR ABSTRACT:"TRIM19" OR TITLE:"RNF71" OR ABSTRACT:"RNF71") 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 PML, not a curated reading list.
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