Summary

Name TRIM28
Full Name Transcription intermediary factor 1-beta
Synonyms TIF1-beta, E3 SUMO-protein ligase TRIM28, 6.3.2.-, KRAB-associated protein 1, KAP-1, KRAB-interacting protein 1, KRIP-1, Nuclear corepressor KAP-1, RING finger protein 96, Tripartite motif-containing protein 28 | KAP1, RNF96, TIF1B
Primary ID Q13263
Links - -
Type protein
Relations 10
Function 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 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). Acts as a corepressor for ZFP568 (By similarity).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ PRKCDdown-regulates img/direct_inhibition.png phosphorylation TRIM28 0.2
Publications: 1 Organism: Homo Sapiens
+ PPP1CAup-regulates activity img/direct-activation.png dephosphorylation TRIM28 0.327
Publications: 1 Organism: Homo Sapiens
+ MAGEA3up-regulates activity img/direct-activation.png binding TRIM28 0.446
Publications: 1 Organism: Homo Sapiens
+ SMARCAD1up-regulates activity img/direct-activation.png binding TRIM28 0.519
Publications: 1 Organism: Homo Sapiens
+ TRIM28up-regulates activity img/direct-activation.png binding MDM2 0.581
Publications: 1 Organism: Homo Sapiens
+ PPP4Cdown-regulates activity img/direct_inhibition.png dephosphorylation TRIM28 0.365
Publications: 1 Organism: Homo Sapiens
+ TRIM28down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation ALDOA 0.2
Publications: 1 Organism: Homo Sapiens
+ MAGEC2up-regulates activity img/direct-activation.png binding TRIM28 0.52
Publications: 1 Organism: Homo Sapiens
+ TRIM28down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation Aldolase 0.2
Publications: 1 Organism: Homo Sapiens
+ TRIM28down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination FBP1 0.314
Publications: 1 Organism: Homo Sapiens