m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03118
 [1]
Histone modification H3K27ac p300 ALKBH5 Indirect Inhibition m6A modification PAK5 PAK5 YTHDF2 : m6A sites
m6A Modification:
m6A Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
m6A Target Serine/threonine-protein kinase PAK 6 (PAK5)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Epigenetic Regulator Histone acetyltransferase p300 (P300) WRITER View Details
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) View Details
Downstream Gene ALKBH5 View Details
Crosstalk Relationship Histone modification  →  m6A Inhibition
Crosstalk Mechanism histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27ac and Histone H3 lysine 4 trimethylation (H3K4me3) histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of Serine/threonine-protein kinase PAK 6 (PAK5). The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Our data provide evidence that E2F1 promotes ALKBH5 transcription by the p300-mediated H3K27ac and WDR5-mediated H3K4me3 mechanisms.
Responsed Disease Cervical cancer ICD-11: 2C77
 Disease Info 
In-vitro Model
 C-33 A Cervical squamous cell carcinoma Homo sapiens CVCL_1094
HeLa Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Ca Ski Cervical squamous cell carcinoma Homo sapiens CVCL_1100
In-vivo Model Tumor xenograft models were established, with each group consisting of 5 mice (n = 5 per group), including ALKBH5, ALKBH5/shPAK5, NC, shCon, shPAK5, shALKBH5, and shALKBH5. Subcutaneous injections of stably transfected HeLa cells (2.0 × 106 cells) were administered into the armpit region of the nude mice.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Histone acetyltransferase p300 (P300) 2 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name CCS1477 Phase 1/2 [2]
Synonyms
CCS-1477; CBP-IN-1; 2222941-37-7; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-((1r,4S)-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one; SCHEMBL20094038; SCHEMBL21515367; SCHEMBL22134021; EX-A3687; NSC818619; NSC-818619; HY-111784; CS-0091862; (S)-1-(3,4-Difluorophenyl)-6-(5-(3,5-dimethylisoxazol-4-yl)-1-(trans-4-methoxycyclohexyl)-1H-benzo[d]imidazol-2-yl)piperidin-2-one
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 134457551
TTD: DIY4C2
 Compound Name FT-7051 Phase 1 [3]
MOA Inhibitor
External Link
TTD: DT8IL6
References
Ref 1 HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5. Pharmacol Res. 2023 Sep;195:106863. doi: 10.1016/j.phrs.2023.106863. Epub 2023 Jul 20.
Ref 2 Targeting the p300/CBP Axis in Lethal Prostate Cancer. Cancer Discov. 2021 May;11(5):1118-1137. doi: 10.1158/2159-8290.CD-20-0751. Epub 2021 Jan 11.
Ref 3 Clinical pipeline report, company report or official report of FORMA Therapeutics.