TRIM24
Description
The TRIM24 (tripartite motif containing 24) is a protein-coding gene located on chromosome 7.
Tripartite motif-containing 24 (TRIM24), also known as transcriptional intermediary factor 1α (TIF1α), is a protein encoded by the TRIM24 gene in humans. It regulates transcription by interacting with the activation function 2 (AF2) region of several nuclear receptors, including estrogen, retinoic acid, and vitamin D3 receptors. TRIM24 localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. It belongs to the tripartite motif (TRIM) family, characterized by 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. TRIM24 interacts with Mineralocorticoid receptor, TRIM33, Estrogen receptor alpha, and Retinoid X receptor alpha.
TRIM24 acts as a transcriptional coactivator, interacting with various nuclear receptors and coactivators to influence gene expression. It binds to chromatin based on histone H3 modifications, exhibiting a strong preference for histone H3 that is unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). TRIM24 possesses E3 protein-ubiquitin ligase activity. During DNA damage repair, it participates in a feedback loop with TP53. Early in response to damage, ATM kinase phosphorylates TRIM24, leading to its ubiquitination and degradation. After adequate repair, TP53 activates TRIM24 transcription, ultimately resulting in TRIM24-mediated ubiquitination and degradation of TP53 (PubMed:24820418). TRIM24 plays a role in regulating cell proliferation and apoptosis, at least in part through its impact on p53/TP53 levels. It upregulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR), and ESR1. It also modulates transcription activation by retinoic acid (RA) receptors, including RARA. TRIM24 is involved in regulating retinoic acid-dependent hepatocyte proliferation (By similarity). It also participates in innate immunity by mediating the specific 'Lys-63'-linked ubiquitination of TRAF3, activating downstream signaling in the type I IFN pathway (PubMed:32324863). Additionally, it negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration, likely by ubiquitinating NLRP3 (PubMed:33724611). {ECO:0000250, ECO:0000269|PubMed:16322096, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:21164480, ECO:0000269|PubMed:24820418, ECO:0000269|PubMed:32324863, ECO:0000269|PubMed:33724611}
TRIM24 is also known as PTC6, RNF82, TF1A, TIF1, TIF1A, TIF1ALPHA, hTIF1.
Associated Diseases
- cancer
- carcinoma of liver and intrahepatic biliary tract
- thyroid gland oncocytic adenoma
- hemangioblastoma
