Copyright
©2014 Baishideng Publishing Group Inc.
World J Biol Chem. Aug 26, 2014; 5(3): 308-320
Published online Aug 26, 2014. doi: 10.4331/wjbc.v5.i3.308
Published online Aug 26, 2014. doi: 10.4331/wjbc.v5.i3.308
Chromatin-associated factors/chromatin-remodeling enzymes | Consequences of binding with KAP1 | Ref. |
HP1 | HP1-KAP1 interaction leads to transcriptional repression and has an essential role in development and cell differentiation. Phosphorylation at Ser-473 or Tyr-449, 458, 517 of KAP1 inhibits its interaction with HP1. | [5,6,33,43,46,53,94-97,105] |
SETDB1 | KAP1 binds to SETDB1 through SUMO:SIM interaction to methylate H3K9 at gene regulatory regions to achieve gene silencing. | [9,15,16,109] |
N-CoR | N-CoR represses basal transcription by the recruitment of HDACs to deacetylate histones. KAP1 is involved in N-CoR-1 complex to mediate transcriptional repression. | [7] |
CHD3 (Mi-2α)/NuRD | NuRD complex mediates chromatin remodelling and histone deacetylation via CHD3 (Mi-2α) and HDACs, respectively. KAP1 interacts with NuRD complex via PHD and bromodomain to alter the chromatin structure. | [8,21,37] |
HDAC1 | KAP1-HDAC1 complex interaction not only regulates histone modification but also non-histone protein deacetylation to exert a variety of different functions (also shown in Table 2). | [113] |
SMARCAD1 | SMARCAD1 mediates histone deacetylation and associates with KAP1-HDAC1 complex to regulate chromatin marks. | [58] |
DNMT | KAP1 associates with DNMT to maintain DNA methylation at imprinting control region (also shown in Table 2). | [59,61] |
Transcription factor | KAP1 function | Ref. |
Myc | KAP1 is involved in MM-1 and HDAC1 complex to suppress c-Myc transcription activity | [10,11] |
ZNF160 | KAP1 interacts with ZNF160 and recruits HDAC to downregulate TLR4 in intestinal epithelial cells | [79] |
Oct3/4 | KAP1 is potentially involved in regulating pluripotency of embryonic stem cells | [78] |
E2F1 | KAP1 suppresses E2F1 transcriptional activity and inhibits E2F1 acetylation in an HDAC1 dependent manner | [13] |
p53 | KAP1 is associated with MDM2-p53-HDAC1 complex and inhibits p53 acetylation and promotes p53 degradation | [75] |
p53 | MAGE proteins stabilize KAP1-p53 complex to decrease acetylation and promote degradation of p53 | [80] |
p53 | KAP1 ubiquitinates p53 for proteasome degradation | [23] |
IRF7 | KAP1 sumolyates IRF7 and suppresses IRF7 transcriptional activity in IFN production | [24] |
ZBRK1 | KAP1 interacts with ZBRK1 to repress Gadd45α and p21 gene expression | [16,17,69] |
HIF-1α | VHLaK potentially recruits KAP1 to HIF-1α complex to suppress HIF-1α downstream gene expression | [72] |
Nrf2 | KAP1 interacts with Nrf2 and facilitates Nrf2 transactivation activity | [76] |
STAT3 | KAP1 interacts with STAT3 to suppress STAT3 transcriptional activity | [82] |
STAT1 | KAP1 interacts with STAT1 to suppress STAT1 transcriptional activity | [50] |
ZNF689 | ZNF689 potentially recruits KAP1 to suppress autophagy-gene-targeting miRNAs | [71] |
FOXP3 | KAP1 is recruited by FIK in FOXP3-FIK-KAP1 complex to suppress FOXP3-target genes | [74] |
NFκB | KAP1 is associated with NFκB and negatively regulates it acetylation and transcriptional activity | [51] |
SRY | KAP1 is recruited by KRAB-O to SRY binding sites for gene regulation | [68,73] |
ZFP57 | ZFP57 and KAP1 are associated with NP95-DNMT complex for maintaining DNA methylation at imprinting control region | [59,61,62] |
Animal model | Phenotype | Ref. |
Kap1 knockout mice | Embryonic lethal prior to gastulation | [19] |
Hemato-specific Kap1 knockout mice | Impaired erythropoiesis | [71,100] |
T-cell-specific Kap1 knockout mice | Defective T-cell differentiation | [48,98] |
B-cell-specific Kap1 knockout mice | Defective B-cell differentiation | [99] |
Tamoxifen-inducible-germ cell-lineage-specific Kap1 depletion mice | Impaired spermatogenesis | [101] |
Liver-specific Kap1 knockout mice | Male-predominant steatosis and hepatic adenoma | [120] |
Kap1 knockout in mice forebrain | Anxiety-like-behavior and cognitive impairments | [103] |
- Citation: Cheng CT, Kuo CY, Ann DK. KAPtain in charge of multiple missions: Emerging roles of KAP1. World J Biol Chem 2014; 5(3): 308-320
- URL: https://www.wjgnet.com/1949-8454/full/v5/i3/308.htm
- DOI: https://dx.doi.org/10.4331/wjbc.v5.i3.308