TRIM24

The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq]

TRIM24

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).

Biological Process calcium ion homeostasis Source:Ensembl
Biological Process cellular response to estrogen stimulus Source:UniProtKB1 Publication
Biological Process epithelial cell proliferation Source:Ensembl
Biological Process negative regulation of DNA-templated transcription Source:Ensembl
Biological Process negative regulation of epithelial cell proliferation Source:Ensembl
Biological Process positive regulation of gene expression Source:Ensembl
Biological Process protein autophosphorylation Source:Ensembl
Biological Process protein catabolic process Source:UniProtKB1 Publication
Biological Process protein ubiquitination Source:UniProtKB1 Publication
Biological Process regulation of apoptotic process Source:UniProtKB1 Publication
Biological Process regulation of protein stability Source:UniProtKB1 Publication
Biological Process regulation of signal transduction by p53 class mediator Source:Ensembl
Biological Process regulation of vitamin D receptor signaling pathway Source:Ensembl
Biological Process transcription by RNA polymerase II Source:ProtInc1 Publication

Nucleus
Cytoplasm
Mitochondrion
Colocalizes with sites of active transcription. Detected both in nucleus and cytoplasm in some breast cancer samples. Predominantly nuclear. Translocated from nucleus to mitochondria to mediate antiviral immunity (PubMed:32324863).

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.

Phosphorylated at Ser-768 by ATM kinase induces ubiquitination and degradation during DNA damage.
Sumoylated.
Undergoes ubiquitination-mediated degradation in response to DNA damage.