Accession PRJCA002417
Title AKT-Mediated Regulation of Chromatin ubiquitination and Tumorigenesis through Mel-18 Phosphorylation
Relevance Medical
Data types Transcriptome or Gene expression
Raw sequence reads
Organisms Homo sapiens
Description Polycomb Repressor Complex 1 (PRC1) is linked to the regulation of gene expression and histone ubiquitination conformation, which contributes to carcinogenesis. However, the upstream regulators of PRC1 biogenesis machineries remain obscure. Here, we reported AKT kinase phosphorylated Mel-18, a polycomb group-related protein, at T334 to disrupt the interaction between Mel-18 and other PRC1 members, leading to attenuated PRC1-dependent ubiquitination of histone H2A at Lys119. As such, PRC1 target genes, many of which are known oncogenes, were de-repression upon T334-Mel18 phosphorylation, which promoted tumor cell growth and metastasis. We depleted Mel-18 using specific single-guide RNAs (sgRNAs) in MDA-MB-231 cells to construct Mel-18-deficient cell model, and then stably added backs through overexpression of Mel18-WT or Mel18-T334A (phosphorylation- deficient mutant). As AKT activity is relatively low in MDA-MB-231 cells, constitutively activated AKT (myr-AKT) was introduced into these cells. ChIP-seq is used to study the difference target genes of Mel18 and H2AK119ub in these two cells.
Sample scope Monoisolate
Release date 2020-08-13
Publication
PubMed ID Article title Journal name DOI Year
33664452 AKT-mediated regulation of chromatin ubiquitylation and tumorigenesis through Mel18 phosphorylation Oncogene 10.1038/s41388-020-01602-7 2021
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) 81772624
National Natural Science Foundation of China (NSFC) 81572605
National Natural Science Foundation of China (NSFC) 81630079
National Natural Science Foundation of China (NSFC) 81972481
National Natural Science Foundation of China (NSFC) 81772835
National Natural Science Foundation of China (NSFC) 81972855
National Natural Science Foundation of China (NSFC) 81803006
the Natural Science Foundation of Guangdong Province 2017A030313481
the Natural Science Foundation of Guangdong Province 2019A1515011209
the Science and Technology Project of Guangzhou 201803010007
the Science and Technology Project of Guangzhou 201707010086
Submitter jia    mai  (834339586@qq.com)
Organization Sun Yat-sen University Cancer Center
Submission date 2020-03-21

Project Data

Resource name Description
BioSample (18)  show -
GSA (3) -
CRA003431 AKT-Mediated Regulation of Chromatin ubiquitination and Tumorigenesis through Mel-18 Phosphorylation
CRA003414 AKT-Mediated Regulation of Chromatin ubiquitination and Tumorigenesis through Mel-18 Phosphorylation
CRA002474 AKT-Mediated Regulation of Chromatin ubiquitination and Tumorigenesis through Mel-18 Phosphorylation