TRIM28

The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM28 Gene(Protein Coding) Tripartite Motif Containing 28

Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754).
Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306).
Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306).
In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity).
Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306).
The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610).
(Microbial infection) Plays a critical role in the shutdown of lytic gene expression during the early stage of herpes virus 8 primary infection. This inhibition is mediated through interaction with herpes virus 8 protein LANA1.

Biological Process chromatin organization Source:UniProtKB-KW
Biological Process convergent extension involved in axis elongation Source:Ensembl
Biological Process DNA methylation involved in embryo development Source:Ensembl
Biological Process DNA repair Source:UniProtKB1 Publication
Biological Process embryo implantation Source:Ensembl
Biological Process embryonic placenta morphogenesis Source:Ensembl
Biological Process epithelial to mesenchymal transition Source:HGNC-UCL
Biological Process innate immune response Source:UniProtKB1 Publication
Biological Process negative regulation of DNA demethylation Source:Ensembl
Biological Process negative regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process negative regulation of single stranded viral RNA replication via double stranded DNA intermediate Source:Ensembl
Biological Process negative regulation of transcription by RNA polymerase II Source:Ensembl
Biological Process positive regulation of DNA binding Source:Ensembl
Biological Process positive regulation of DNA methylation-dependent heterochromatin assembly Source:UniProtKB1 Publication
Biological Process positive regulation of DNA repair Source:UniProtKB1 Publication
Biological Process positive regulation of DNA-templated transcription Source:HGNC-UCL
Biological Process positive regulation of protein import into nucleus Source:UniProtKB1 Publication
Biological Process protein autophosphorylation Source:Ensembl
Biological Process protein sumoylation Source:UniProtKB1 Publication
Biological Process Ras protein signal transduction Source:UniProtKB1 Publication
Biological Process regulation of genetic imprinting Source:Ensembl
Biological Process suppression of viral release by host Source:UniProtKB1 Publication

Nucleus
Associated with centromeric heterochromatin during cell differentiation through CBX1.

ATM-induced phosphorylation on Ser-824 represses sumoylation leading to the de-repression of expression of a subset of genes involved in cell cycle control and apoptosis in response to genotoxic stress. Dephosphorylation by the phosphatases, PPP1CA and PP1CB forms, allows sumoylation and expression of TRIM28 target genes.
Sumoylation/desumoylation events regulate TRIM28-mediated transcriptional repression. Sumoylation is required for interaction with CHD3 and SETDB1 and the corepressor activity. Represses and is repressed by Ser-824 phosphorylation. Enhances the TRIM28 corepressor activity, inhibiting transcriptional activity of a number of genes including GADD45A and CDKN1A/p21. Lys-554, Lys-779 and Lys-804 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-824 prevents sumoylation and allows de-repression of CDKN1A/p21.
Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2.
Citrullinated by PADI4.
ADP-ribosylated by SIRT6, promoting TRIM28/KAP1 interaction with CBX5, thereby contributing to the packaging of LINE-1 retrotransposon elements into transcriptionally repressive heterochromatin.