Kat5 antibody - N-terminal region (ARP40066_P050)
- Known as:
- Kat5 (anti-) - N-terminal region (ARP40066_P050)
- Catalog number:
- arp40066_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- Kat5 antibody - N-terminal region (ARP40066_P050)
Related genes to: Kat5 antibody - N-terminal region (ARP40066_P050)
- Gene:
- KAT5 NIH gene
- Name:
- lysine acetyltransferase 5
- Previous symbol:
- HTATIP
- Synonyms:
- TIP60, PLIP, cPLA2, HTATIP1, ESA1, ZC2HC5
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2000-04-13
- Date modifiied:
- 2016-10-05
Related products to: Kat5 antibody - N-terminal region (ARP40066_P050)
Related articles to: Kat5 antibody - N-terminal region (ARP40066_P050)
- Prostate adenocarcinomas (PRAD) can acquire resistance to androgen receptor signaling inhibitors through lineage transition to a cell state known as neuroendocrine prostate cancer (NEPC). Using a panel of isogenic PRAD and NEPC mouse tumoroids, we show that NEPC cells acquire new transcription factor (TF) dependencies that function in a previously undefined network. Through selective perturbation of each TF, we identify ASCL1 as a key regulator of NE lineage fate whereas MYCL functions downstream to drive NEPC growth/survival by recruitment of the TIP60/KAT5 acetyltransferase. Interestingly, while dependencies on specific TF family paralogs can vary across NEPC models, all show markedly enhanced dependency on TIP60. Moreover, the H2A.Z-acetyltransferase activity of the TIP60 complex (TIP60-C) is required for NEPC as well as the acetyl-reader BRD8, which is newly incorporated as a TIP60-C subunit with the NEPC transition. Targeted degradation studies in isogenic tumoroids reveal increased dependence on MYCL in NEPC relative to its paralog MYC in PRAD. In addition to a paralog switch (MYC to MYCL), the MYC pathway-addicted NE state is accompanied by a chaperone switch (from TIP60-C to SRCAP) for H2A.Z histone exchange and a coactivator switch (to TIP60) for MYC target gene expression. The NE-specific coupling of MYCL with TIP60 reveals a previously unappreciated opportunity to target MYC-driven NE diseases through pharmacological inhibition of TIP60. - Source: PubMed
Publication date: 2026/05/08
Sun ZhenZhao Jimmy LKhan Zahra FIsmail Wazim MHan TengNandakumar SubhikshaYoung SerinaLange MatthewCheng PanKoche RichardSchultz NikolausGaspar-Maia AlexandreSawyers Charles L - Aortic aneurysm (AA) is a life-threatening vascular disorder characterized by smooth muscle cell (SMC) phenotypic switching. However, SMC heterogeneity and the regulatory mechanisms underlying this transition remain incompletely understood. - Source: PubMed
Publication date: 2026/05/14
Zhang JianlinZhao Wenbo - MYST lysine acetyltransferases (KATs) are a class of epigenetic enzymes critical for cellular function that constitute an emerging therapeutic target in cancer. Recently, several drug-like MYST inhibitors have been reported that show promise in preclinical models as well as in clinical trials of breast cancer. Understanding the specificity of these molecules is critical for their effective use as chemical probes. Here we apply an integrated profiling strategy to systematically define the potency and selectivity of drug-like MYST KAT inhibitors. First, we use optimized chemoproteomic profiling and histone acetylation biormarkers to study the industry-developed KAT inhibitor PF-9363. This reveals dose-dependent engagement of native KAT complexes, with hierarchical inhibition following the order KAT6A/B > KAT7 » KAT8 > KAT5. This pattern of target engagement is shared by the clinical candidate PF-8144. Next, we demonstrate how PF-9363's ability to disrupt capture of MYST complex members in chemoproteomic experiments can be leveraged to identify uncharacterized candidate members of these complexes, including the transcription factor FOXK2. Applying insights from these studies to WM-8014, WM-1119 and WM-3835, which have been extensively applied in the literature as MYST probes, highlights unexpected cross-inhibition and suggests a framework for how these small molecules and biomarkers may be applied to differentiate KAT6A/B and KAT7-dependent phenotypes. Finally, we benchmark the activity of PF-9363 in the NCI-60 cell line screen, providing evidence that its ability to engage KAT8 at elevated concentrations can drive acute growth inhibition. Collectively, our studies indicate the potential for MYST KAT inhibitors, including clinical candidates, to exhibit dose-dependent target engagement reminiscent of kinase inhibitors. The assays and biomarkers described here should find broad utility in assessing selective target engagement by this inhibitor class. - Source: PubMed
Publication date: 2026/05/13
Chen XueminCastroverde AlexandraPerez MinervoHolewinski RonaldSuazo Kiall FKarki RashmiAndresson ThorkellGarcia Benjamin AMeier Jordan L - Chromatin modifiers regulate genome function by modulating chromatin structure and are essential for processes such as transcription, DNA repair, and cell division. The lysine acetyltransferase TIP60 (KAT5), a member of the MYST family, is a key regulator of chromatin dynamics and has established roles in stem cell maintenance and differentiation, however its function in regeneration remains unclear. Here, we investigated the role of the TIP60 homolog (SMED-TIP60) in the planarian Schmidtea mediterranea, a model system for stem cell-driven regeneration. Biochemical analyses demonstrated that SMED-TIP60 possesses both histone acetyltransferase and autoacetylation activities. Functional depletion of Smed-tip60 by RNA interference impaired tissue homeostasis and survival. Regeneration assays revealed severe defects in blastema formation, culminating in a complete failure of regeneration upon TIP60 loss. Mechanistically, in situ hybridization and immunofluorescence analyses showed a marked reduction in stem cell populations and proliferation in Smed-tip60 RNAi animals. Injury-induced expression of SMED-TIP60 peaked at 5 days post-amputation, and transcriptomic (RNA-seq) analysis revealed widespread dysregulation of gene expression at both anterior and posterior wound sites, with increased transcriptional perturbation correlating with elevated TIP60 levels. Furthermore, key wound-response genes were aberrantly expressed in Smed-tip60-depleted animals, indicating disruption of the injury-response program and positional information resetting. Collectively, these findings identify TIP60 as an essential regulator of stem cell-mediated regeneration, functioning to coordinate wound-response gene expression and tissue restoration. - Source: PubMed
Publication date: 2026/05/11
Pal AkanshaArora AnkitKumar HemantThokchom AnnaJaiswal BhartiPalakodeti DasaradhiGupta Ashish - Cisplatin, a highly effective chemotherapeutic agent, is subject to significant clinical limitations due to its dose-limiting nephrotoxicity, which can result in acute kidney injury (AKI) and chronic kidney disease. The present study investigates the renoprotective potential of Astragaloside IV (AS-IV), a primary bioactive component of Astragalus membranaceus, against cisplatin-induced nephrotoxicity (CIAKI) and elucidates its underlying molecular mechanism. In a murine model, AS-IV treatment was demonstrated to significantly ameliorate cisplatin-induced renal dysfunction, histopathological damage, and the upregulation of markers associated with inflammation and fibrosis. Utilising network pharmacology and molecular docking methodologies, we have identified the pyroptosis pathway as a pivotal target of AS-IV. Subsequent mechanistic studies revealed that AS-IV specifically inhibits NLRP3 inflammasome-mediated pyroptosis. This inhibition occurs via potential binding of AS-IV to the lysine acetyltransferase KAT5 (Tip60), thereby suppressing KAT5 expression and its catalytic activity. Consequently, AS-IV has been demonstrated to impede KAT5-mediated acetylation of NLRP3 at the K24 residue, a critical step for inflammasome assembly and activation. The present study elucidates a hitherto unobserved mechanism by which AS-IV mitigates CIAKI, through the potential targeting of the KAT5/NLRP3 acetylation axis to inhibit pyroptosis. This work provides novel insights into the pathogenesis of cisplatin-induced nephrotoxicity and positions AS-IV as a promising therapeutic candidate for preventing and treating this serious side effect. - Source: PubMed
Publication date: 2026/05/06
Qian YiHong PanpanYing YijianXie ShuaiZheng Yumei