Function TRIM28

1 function

1.1 cellular differentiation , proliferation
1.2 transcriptional regulation
1.3 dna damage repair response
1.4 apoptosis

function

the protein encoded gene mediates transcriptional control interaction krüppel-associated box repression domain found in many transcription factors. protein localizes nucleus , thought associate specific chromatin regions. protein member of tripartite motif family. tripartite motif includes 3 zinc-binding domains, ring, b-box type 1 , b-box type 2, , coiled-coil region.

kap1 ubiquitously expressed protein involved in many critical functions including: transcriptional regulation, cellular differentiation , proliferation, dna damage repair, viral suppression, , apoptosis.(4) functionality dependent upon post-translational modifications. phosphorylation of kap1 acts deactivator of protein in many of mechanisms while sumoylation acts activator.

cellular differentiation , proliferation

studies have shown deletion of kap1 in mice before gastrulation results in death (implicating necessary protein proliferation) while deletion in adult mice results in increased anxiety , stress-induced alterations in learning , memory. kap1 has been shown participate in maintenance of pluripotency of embryonic stem cells , promote , inhibit cellular differentiation of adult cell lines. increased levels of kap1 have been found in liver, gastric, breast, lung, , prostate cancers well, indicating may play important role in tumor cell proliferation (possibly inhibiting apoptosis).

transcriptional regulation

kap1 can regulate genomic transcription through variety of mechanisms, many of remain unclear. studies have shown kap1 can repress transcription binding directly genome (which can sufficient in , of itself) or through induction of heterochromatin formation via mi2α-setb1-hp1 macromolecular complex. kap1 can interact histone methyltransferases , deacetylases via c-terminal phd , bromodomain control transcription epigenetically.

dna damage repair response

it has been shown atm phosphorylates kap1 upon discovery of damaged or broken dna. phosphorylated kap1, along many other dna damage proteins, rapidly migrate site of dna damage. exact involvement in pathway unclear, has been implicated in triggering cell arrest, allowing damaged dna repaired.

apoptosis

kap1 forms complex mdm2 (a ubiquitin e3 ligase) binds p53. complex marks bound p53 degradation. p53 known precursor of apoptosis facilitates synthesis of proteins necessary cell death degradation results in apoptosis inhibition.