TRIM28 is a multifunctional protein that plays a crucial role in various cellular processes. It mediates transcriptional control by interacting with the Krüppel-Associated Box (KRAB) repression domain found in many transcription factors . The protein localizes to the nucleus and is thought to associate with specific chromatin regions .
The functionality of TRIM28 is dependent on post-translational modifications. For instance, sumoylated TRIM28 can assemble epigenetic machinery for gene silencing, while phosphorylated TRIM28 is involved in DNA repair .
TRIM28 is involved in several critical functions, including:
Transcriptional Regulation: TRIM28 can regulate genomic transcription through various mechanisms. It can repress transcription by binding directly to the genome or through the induction of heterochromatin formation via the Mi2α-SETB1-HP1 macromolecular complex . It also interacts with histone methyltransferases and deacetylases to control transcription epigenetically .
Cellular Differentiation and Proliferation: Studies have shown that deletion of KAP1 in mice before gastrulation results in death, implicating it as a necessary protein for proliferation . In adult mice, deletion results in increased anxiety and stress-induced alterations in learning and memory . TRIM28 participates in the maintenance of pluripotency of embryonic stem cells and promotes or inhibits cellular differentiation of adult cell lines .
DNA Damage Repair: Phosphorylated TRIM28 is involved in the DNA damage response, helping to maintain genome stability .
Viral Suppression and Apoptosis: TRIM28 is involved in viral suppression and apoptosis, contributing to the cellular defense mechanisms .
TRIM28 has been extensively studied for its role in cancer biology. It is known to participate in many aspects of cellular biology, either promoting cell proliferation or mediating anti-proliferative activities . The protein is involved in the regulation of gene expression through heterochromatin formation, mediation of DNA damage response, inhibition of p53 activity through intrinsic E3 ubiquitin ligase activity, regulation of epithelial to mesenchymal transition (EMT), maintenance of stem cell pluripotency, and regulation of autophagy .
Studies have shown significant upregulation of TRIM28 expression in cancer tissues, which correlates with worse overall patient survival, suggesting that TRIM28 supports cancer progression . The complexity of TRIM28’s involvement in cancer biology makes it a potential candidate for targeted anti-cancer therapy .