Asset Details
Do you wish to reserve the book?
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL
Do you wish to request the book?
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL
2017
Overview
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively kill tumor cells. TRAIL resistance in cancers is associated with aberrant expression of the key components of the apoptotic program. However, how these components are regulated at the epigenetic level is not understood. In this study, we investigated novel epigenetic mechanisms regulating TRAIL response in glioblastoma multiforme (GBM) cells by a short-hairpin RNA loss-of-function screen. We interrogated 48 genes in DNA and histone modification pathways and identified KDM2B, an H3K36-specific demethylase, as a novel regulator of TRAIL response. Accordingly, silencing of KDM2B significantly enhanced TRAIL sensitivity, the activation of caspase-8, -3 and -7 and PARP cleavage. KDM2B knockdown also accelerated the apoptosis, as revealed by live-cell imaging experiments. To decipher the downstream molecular pathways regulated by KDM2B, levels of apoptosis-related genes were examined by RNA-sequencing upon KDM2B loss, which revealed derepression of proapoptotic genes Harakiri (
HRK
),
caspase-7
and death receptor 4 (
DR4
) and repression of antiapoptotic genes. The apoptosis phenotype was partly dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. KDM2B-silenced tumors exhibited slower growth
in vivo.
Taken together, our findings suggest a novel mechanism, where the key apoptosis components are under epigenetic control of KDM2B in GBM cells.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 38
/ 42/89
/ 82/80
/ 96/2
/ Apoptosis Regulatory Proteins - genetics
/ Biomedical and Life Sciences
/ Caspase
/ Death
/ DNA
/ Enzymes
/ Epigenesis, Genetic - genetics
/ Gene Expression Regulation, Neoplastic - genetics
/ Humans
/ Jumonji Domain-Containing Histone Demethylases - genetics
/ Original
/ Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics
/ RNA
/ RNA, Small Interfering - genetics
/ TNF-Related Apoptosis-Inducing Ligand - administration & dosage
/ TNF-Related Apoptosis-Inducing Ligand - genetics
/ Tumors
