Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma.
Epigenetics
Histone modifications
JQKD82
KDM5 inhibitor
Multiple myeloma
Transcription factor
Journal
Blood cancer discovery
ISSN: 2643-3249
Titre abrégé: Blood Cancer Discov
Pays: United States
ID NLM: 101764786
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
entrez:
14
7
2021
pubmed:
15
7
2021
medline:
15
3
2022
Statut:
ppublish
Résumé
Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3K4 trimethylation, a histone mark associated with activate gene transcription. We identify that KDM5A interacts with the P-TEFb complex and cooperates with MYC to control MYC targeted genes in multiple myeloma (MM) cells. We develop a cell-permeable and selective KDM5 inhibitor, JQKD82, that increases histone H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output
Identifiants
pubmed: 34258103
doi: 10.1158/2643-3230.BCD-20-0108
pmc: PMC8265280
mid: NIHMS1688764
pii: 2643-3230.BCD-20-0108
doi:
Substances chimiques
MYC protein, human
0
Proto-Oncogene Proteins c-myc
0
KDM5A protein, human
EC 1.14.11.-
Retinoblastoma-Binding Protein 2
EC 1.14.11.27
Cyclin-Dependent Kinase 9
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
RNA Polymerase II
EC 2.7.7.-
Lysine
K3Z4F929H6
Cyclin-Dependent Kinase-Activating Kinase
EC 2.7.11.22
CDK7 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
370-387Subventions
Organisme : NCI NIH HHS
ID : K08 CA245251
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100707
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA233601
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA236754
Pays : United States
Déclaration de conflit d'intérêts
DECLARATION OF INTERESTS J.Q. is scientific co-founder and consultant of Epiphanes. Other authors declare no potential conflicts of interest.
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