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Catalytic subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. Also acetylates non-histone proteins, such as ATM, NR1D2, RAN, FOXP3, ULK1 and RUBCNL/Pacer. Directly acetylates and activates ATM. Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2. Promotes FOXP3 acetylation and positively regulates its transcriptional repressor activity. Acetylates RAN at 'Lys-134'. Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy: phosphorylated at Ser-86 by GSK3 under starvation conditions, leading to activate acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer.
基因功能參考文獻:
Results show that KAT5 expression is decreased in prostate cancer (PCa) and correlated with shorter recurrence-free survival. PMID: 30142696
Tip60 suppressed growth and metastasis throughout the progression of cholangiocarcinoma and identified the PI3K/AKT pathway as a dominant signal of Tip60. PMID: 30308494
TIP60 is involved in several adipogenesis mechanisms through its interaction with three important proteins: PPARc, USP7, and GPR50. These actors act also in different processes of breast cancer development. PMID: 28873018
These findings demonstrate the critical regulation of TIP60/p53 pathway in apoptosis upon metabolic stress and provide a novel insight into the down-regulation of TIP60 in tumor cells. PMID: 29174981
Our data demonstrate for the first time that TIP60 through its MYST domain directly interacts with UHRF1 PMID: 29268763
These results suggest that TIP60, in concert with other cellular factors, plays an important role in the regulation of the HBV chromatin structure by acting as a critical component of the intrinsic antiviral defense, which sheds new light on the regulation of HBV replication. PMID: 29321313
Irreversible inhibition of USP7 results in durable downstream biological responses in cells, including down-regulation of Tip60 and consequent impairment of Treg suppressive function PMID: 29236775
most HIF1A targets require either TIP60, the CDK8-Mediator complex, or both as coactivators for full expression in hypoxia. PMID: 27320910
NOTCH1 inhibits activation of ATM by impairing the formation of an ATM-FOXO3a-KAT5 complex. PMID: 27524627
Collectively, the data establish a hitherto unknown liaison among MDR1, BMI1 and TIP60 and provide mechanistic insights into cisplatin-induced MDR1 expression resulting in acquired cross-resistance against paclitaxel, doxorubicin and likely other anticancer drugs. PMID: 27295567
TIP60-mediated growth suppression of HPV-induced cervical cancer is mediated in part due to TERT repression through Sp1 acetylation. In summary, our study has identified a novel substrate for TIP60 catalytic activity and a unique repressive mechanism acting at the TERT promoter in virus-induced malignancies. PMID: 29045464
These findings reveal that Endoplasmic reticulum stress engages the GSK3beta-TIP60-ULK1 pathway to increase autophagy. PMID: 28032867
TIP60 complex regulates bivalent chromatin recognition/modification by 53BP1 through direct H4K20me binding and H2AK15 acetylation. PMID: 27153538
Studies suggest that lysine (K) acetyltransferase inhibitors (KATi) are important for providing personalized therapies. PMID: 27528742
Thus Tip60 interacts with RNR and NME3 to provide site-specific synthesis of dNTP for facilitating DNA repair in serum-deprived cells which contain low levels of dNTPs. PMID: 26945015
TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. PMID: 27743347
Data provide evidence that the acetylation of H2AX at Lys5 by TIP60 is required for the (ADPribosyl) ation activity and the dynamic binding of PARP-1 to chromatin after the induction of DNA damage. PMID: 26976643
Synthetic lethality screening identifies TIP60-dependent radiation sensitivity in the absence of BAF180. PMID: 27461052
E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A. PMID: 27664947
UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. PMID: 26994140
KAT5 is significantly elevated in malignant pleural mesothelioma PMID: 26780987
Data suggest the combination of histone acetyltransferase TIP60 and microRNA miR-22 as prognostic indicator of breast cancer progression. PMID: 26512777
Colony-formation assays and soft agar assays show that gain of function of TIP60 or depletion of EDD1 in HPV-positive cervical cancer cells significantly inhibits cell growth in vitro PMID: 26234678
We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells PMID: 26464124
TIP60 relocalization to the chromatin to acetylates histone H4K16 and prevents the binding of 53BP1 to its docking site.Impaired TIP60-mediated H4K16 acetylation accounts for the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia. PMID: 26446986
Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA. PMID: 26420831
the acetylation-dependent NBS1 turnover by TIP60 on damaged chromatin restricts the dispersal of NBS1 foci from the sites of DNA damage. PMID: 26438602
The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60 stability by promoting USP7-mediated deubiquitination of Tip60. PMID: 25865756
Putative novel MYC interactors include components of the STAGA/KAT5 and SWI/SNF chromatin remodeling complexes PMID: 25452129
TIP60 interacted with H3K4me3 in response to TNF-alpha signaling. PMID: 25560918
Results establish that Tip60-T158 phosphorylation by p38 plays an essential role in stimulating Tip60 activity required for inducing the p53-PUMA pathway that ultimately leads to apoptosis in response to DNA damage. PMID: 25544752
Tip60 is an important regulator of human papillomavirus genome amplification whose activity during the viral life cycle is controlled by STAT-5 and the kinase GSK3beta. PMID: 25673709
HDAC3 promotes TIP60 ubiquitination and cytoplasmic localization and protects cells from apoptosis after DNA damage. PMID: 25301942
These findings suggest that E2 recruits histone-modifying cellular proteins to the HPV LCR, resulting in transcriptional repression of E6 and E7. PMID: 25222147
that KAT5 RNAi may result in cleaved casp9 upregulation through p38MAPK activation in Gallbladder carcinoma cells PMID: 24427328
KAT5 and KAT6B regulate prostate cancer cell growth through PI3K-AKT signaling. PMID: 24294372
Human melanoma patient samples and cell lines maintain p53 expression but PIASy and/or Tip60 are frequently lost. PMID: 23624367
degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes PMID: 23178490
Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERbeta1 to the cis-regulatory regions. PMID: 23857583
USP7 deubiquitinase activity is required for the stabilization of Tip60 in order to operate an effective p53-dependent apoptotic pathway in response to genotoxic stress. PMID: 23775119
we conclude that PPAR agonists used in this work induces M1 macrophages polarization via inhibition of cPLA2 and the increase of aggressive microbicidal activity via reactive oxygen species (ROS) production. PMID: 23555077
The role of Tip60 in mediating acetylation of p21 at its C-terminus is a novel and significant mechanism for post-translational regulation of cell-cycle progression. PMID: 23238566
UHRF1 is a critical negative regulator of TIP60 and suggest that UHRF1-mediated effects on p53 may contribute, at least in part, to its role in tumorigenesis. PMID: 23677994
study shows Tip60 plays an essential role in oncogenic ras-induced senescence; revealed a cascade of posttranslational modifications involving p38, Tip60 and PRAK, 3 proteins essential for ras-induced senescence; these modifications are critical for prosenescent function of Tip60 and PRAK PMID: 23685072
Data indicate that ING5 associates with Tip60 (KAT5) to form a complex with p53. PMID: 23576563
a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNgamma production, which could contribute to the regulation of inflammation. PMID: 23609452
RVBs are also required for heat stability of TIP60.com by a p400-independent pathway. PMID: 23297341
tyrosine phosphorylation of KAT5 increases after DNA damage in a manner that promotes KAT5 binding to the histone mark H3K9me3; this triggers KAT5-mediated acetylation of the ATM kinase, promoting DNA-damage-checkpoint activation and cell survival PMID: 23708966
Studies indicate histone acetyltransferase Tip60 as a potential therapeutic target for the treatment of prostate cancer. PMID: 23056207
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亞細胞定位:
Nucleus. Nucleus, nucleolus. Cytoplasm, perinuclear region. Note=Upon stimulation with EDN1, it is exported from the nucleus to the perinuclear region and UV irradiation induces translocation into punctuate subnuclear structures named nuclear bodies.