TRIM24
Function
Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. During the DNA damage response, participates in an autoregulatory feedback loop with TP53. Early in response to DNA damage, ATM kinase phosphorylates TRIM24 leading to its ubiquitination and degradation. After sufficient DNA repair has occurred, TP53 activates TRIM24 transcription, ultimately leading to TRIM24-mediated TP53 ubiquitination and degradation (PubMed:24820418). Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity). Participates also in innate immunity by mediating the specific 'Lys-63'-linked ubiquitination of TRAF3 leading to activation of downstream signal transduction of the type I IFN pathway (PubMed:32324863). Additionally, negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration probably by ubiquitinating NLRP3 (PubMed:33724611).
Involvement in disease
A chromosomal aberration involving TRIM24/TIF1 is found in papillary thyroid carcinomas (PTCs). Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Phosphorylated at Ser-768 by ATM kinase induces ubiquitination and degradation during DNA damage.
Sumoylated.
Undergoes ubiquitination-mediated degradation in response to DNA damage.
Cellular localization
- Nucleus
- Cytoplasm
- Mitochondrion
- Colocalizes with sites of active transcription. Predominantly nuclear. Translocated from nucleus to mitochondria to mediate antiviral immunity (PubMed:32324863). Localizes to sites of DNA damage (PubMed:25593309).
Alternative names
RNF82, TIF1, TIF1A, TRIM24, Transcription intermediary factor 1-alpha, TIF1-alpha, E3 ubiquitin-protein ligase TRIM24, RING finger protein 82, RING-type E3 ubiquitin transferase TIF1-alpha, Tripartite motif-containing protein 24