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    GENE:

    KAT6A (Lysine Acetyltransferase 6A)

    i
    Other names: KAT6A, Lysine Acetyltransferase 6A, MOZ, Monocytic Leukemia Zinc Finger Protein, ZC2HC6A, RUNXBP2, ZNF220, MYST3, MYST Histone Acetyltransferase (Monocytic Leukemia) 3, Runt-Related Transcription Factor Binding Protein 2, MOZ, YBF2/SAS3, SAS2 And TIP60 Protein 3, Histone Acetyltransferase KAT6A, K(Lysine) Acetyltransferase 6A, Zinc Finger Protein 220, MYST-3, Runt-Related Transcription Factor-Binding Protein 2, Histone Acetyltransferase MYST3, ARTHS, MRD32
    17d
    KAT6A acetyltransferase accelerates colorectal cancer progression through upregulating BRD1 protein expression via acetylation modification. (PubMed, Cancer Cell Int)
    Collectively, our research demonstrated that KAT6A upregulates BRD1 protein expression through acetylation, thereby promoting CRC progression. These results suggest KAT6A-mediated BRD1 acetylation as a novel and promising therapeutic target for CRC, contributing valuable insights into the molecular mechanisms underlying CRC pathogenesis.
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    KAT6A (Lysine Acetyltransferase 6A)
    1m
    KAT6A regulates osteoclast differentiation and bone resorption through TET1-mediated TRPV4 expression. (PubMed, Naunyn Schmiedebergs Arch Pharmacol)
    Overexpression of either Tet1 or TRPV4 rescued the KAT6A knockdown-induced osteoclast differentiation inhibition. KAT6A promotes osteoclast differentiation through a regulatory cascade involving Tet1-mediated TRPV4 upregulation, which identifying KAT6A as a potential therapeutic target for osteoporosis treatment.
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    TET1 (Tet Methylcytosine Dioxygenase 1) • KAT6A (Lysine Acetyltransferase 6A) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2) • TRPV4 (Transient Receptor Potential Cation Channel Subfamily V Member 4)
    2ms
    Breaking Barriers in Breast Cancer: Multi-Targeted Therapeutic Insights. (PubMed, Mini Rev Med Chem)
    The future of breast cancer therapy lies in combination strategies that are developed via molecular profiling and guided by resistance biomarkers. Integrative, biomarker-driven treatment approaches will provide a rationalized and likely more effective means of treating advanced and refractory breast cancer in our effort to improve patient outcomes in a targeted and personalized approach.
    Journal • PARP Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • KAT6A (Lysine Acetyltransferase 6A)
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    Ibrance (palbociclib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    2ms
    Hierarchical small molecule inhibition of MYST acetyltransferases. (PubMed, bioRxiv)
    Finally, we benchmark the activity of PF-9363 in the NCI-60 cell line screen, providing evidence that it can inhibit the growth of cell lines that are resistant to other epigenetic inhibitors by engaging the essential MYST enzyme KAT8 at high concentrations. Collectively, our studies indicate the potential for MYST KAT inhibitors to exhibit dose-dependent target engagement reminiscent of kinase inhibitors and specify assays and biomarkers for facile monitoring of selective and hierarchical effects.
    Journal
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    KAT6A (Lysine Acetyltransferase 6A)
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    CTx-648
    2ms
    Correlation between KAT6A and PD-L1 expression and role of KAT6A in colorectal cancer. (PubMed, World J Gastrointest Oncol)
    KAT6A drives CRC progression and immune evasion by promoting histone H3 propionylation to epigenetically activate PD-L1 expression. Targeting KAT6A or its downstream H3K23pr-PD-L1 axis represents a promising therapeutic strategy to overcome ICI resistance in CRC.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • GZMB (Granzyme B) • KAT6A (Lysine Acetyltransferase 6A) • PRF1 (Perforin 1)
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    PD-L1 expression
    4ms
    KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML. (PubMed, Genome Biol)
    Our study identifies a self-reinforcing epigenetic module of histone modifiers and readers in KAT6A-rearranged AML, providing mechanistic insights into the genomic targeting of KAT6A chimeras and highlighting promising combinatorial therapeutic strategies.
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    KAT6A (Lysine Acetyltransferase 6A)
    4ms
    Haploidentical Hematopoietic Stem Cell Transplantation With Ex Vivo TCR Alpha/Beta and CD19 Depletion in Pediatric Hematologic Malignancies (clinicaltrials.gov)
    P1, N=50, Recruiting, Washington University School of Medicine | N=32 --> 50 | Trial completion date: Nov 2027 --> May 2029 | Trial primary completion date: Nov 2027 --> May 2029
    Enrollment change • Trial completion date • Trial primary completion date
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CD38 (CD38 Molecule) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • AFF1 (AF4/FMR2 Family Member 1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • NCAM1 (Neural cell adhesion molecule 1) • NUP214 (Nucleoporin 214) • TCF3 (Transcription Factor 3) • FUS (FUS RNA Binding Protein) • HLA-B (Major Histocompatibility Complex, Class I, B) • KAT6A (Lysine Acetyltransferase 6A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • EGR1 (Early Growth Response 1) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    4ms
    Inhibition of KAT6A Enhances Immunotherapy Efficacy in Colorectal Cancer by Activating Interferon Response. (PubMed, Cancer Lett)
    Furthermore, in a cohort of CRC patients receiving immunotherapy, we showed that high KAT6A expression correlated with impaired treatment response, manifested by lower objective response rates, shorter progression-free survival (PFS), and decreased overall survival (OS). Importantly, this study reveals KAT6A's pivotal role in modulating CRC immune evasion via regulating endogenous IFN response of tumor cells, thereby establishing its potential as a therapeutic target for enhancing immunotherapy efficacy in CRC.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • DNMT1 (DNA methyltransferase 1) • KAT6A (Lysine Acetyltransferase 6A)
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    MSI-H/dMMR
    5ms
    KAT6A Promotes Macrophage Inflammation and Periodontitis. (PubMed, J Clin Periodontol)
    Furthermore, using the Cut&tag technique, we identified reduced histone H3K27 acetylation levels at nuclear factor kappa-B binding sites on promoters of interleukin 1β and tumour necrosis factor in MK6AKO macrophages treated with Pg-LPS. In summary, our study highlights the significant role of KAT6A in modulating macrophage phenotypes and the progression of PD, suggesting the therapeutic potential of targeting KAT6A.
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    IL17A (Interleukin 17A) • KAT6A (Lysine Acetyltransferase 6A) • IL1B (Interleukin 1, beta)
    5ms
    KAT6A/B inhibition synergizes with retinoic acid and enhances the efficacy of GD2-targeted immunotherapy in neuroblastoma. (PubMed, bioRxiv)
    Moreover, PF-9363 plus retinoids increases GD2 expression, rendering neuroblastoma cells more sensitive to anti-GD2 immunotherapy. Overall, our studies demonstrate that KAT6A/B inhibition increases the effectiveness of retinoids and GD2-targeted immunotherapy in neuroblastoma.
    Journal • IO biomarker
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    MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • KAT6A (Lysine Acetyltransferase 6A) • GATA3 (GATA binding protein 3) • PHOX2B (Paired Like Homeobox 2B)
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    CTx-648