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 |