PMID- 22065586
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 1
DP  - 2012 Jan 2
TI  - Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression 
      through co-activation of ERK and JNK signaling.
PG  - 257-267
LID - S0021-9258(20)53510-2 [pii]
LID - 10.1074/jbc.M111.304006 [doi]
AB  - Oncogenic mutations of ras and B-raf frequently occur in many cancer types and 
      are critical for cell transformation and tumorigenesis. Death receptor 5 (DR5) is 
      a cell surface pro-apoptotic death receptor for tumor necrosis factor-related 
      apoptosis-inducing ligand and has been targeted in cancer therapy. The current 
      study has demonstrated induction of DR5 expression by the oncogenic proteins Ras 
      and B-Raf and revealed the underlying mechanisms. We demonstrated that both Ras 
      and B-Raf induce DR5 expression by enforced expression of oncogenic Ras (e.g. 
      H-Ras12V or K-Ras12V) or B-Raf (i.e. V600E) in cells and by analyzing gene 
      expression array data generated from cancer cell lines and from human cancer 
      tissues. This finding is further supported by our results that knockdown of 
      endogenous K-Ras or B-Raf (V600E) reduced the expression of DR5. Importantly, we 
      have elucidated that Ras induces DR5 expression through co-activation of ERK/RSK 
      and JNK signaling pathways and subsequent cooperative effects among the 
      transcriptional factors CHOP, Elk1, and c-Jun to enhance DR5 gene transcription. 
      Moreover, we found that the majority of cancer cell lines highly sensitive to the 
      DR5 agonistic antibody AMG655 have either Ras or B-Raf mutations. Our findings 
      warrant further study on the biology of DR5 regulation by Ras and B-Raf, which 
      may provide new insight into the biology of Ras and B-Raf, and on the potential 
      impact of Ras or B-Raf mutations on the outcome of DR5-targeted cancer therapy.
FAU - Oh, You-Take
AU  - Oh YT
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322.
FAU - Yue, Ping
AU  - Yue P
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322.
FAU - Balko, Justin M
AU  - Balko JM
AD  - Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
FAU - Black, Esther P
AU  - Black EP
AD  - Department of Pharmaceutical Sciences, University of Kentucky, Lexington, 
      Kentucky 40536.
FAU - Owonikoko, Taofeek K
AU  - Owonikoko TK
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322.
FAU - Khuri, Fadlo R
AU  - Khuri FR
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322.
FAU - Sun, Shi-Yong
AU  - Sun SY
AD  - Department of Hematology and Medical Oncology, Emory University School of 
      Medicine and Winship Cancer Institute, Atlanta, Georgia 30322. Electronic 
      address: ssun@emory.edu.
LA  - eng
GR  - K23 CA164015/CA/NCI NIH HHS/United States
GR  - P50 CA128613/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20111107
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DDIT3 protein, human)
RN  - 0 (ELK1 protein, human)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
EIN - J Biol Chem. 2020 Jun 26;295(26):8870. PMID: 32591446
MH  - Cell Line, Tumor
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutation
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics/*metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*genetics/immunology
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - *Signal Transduction
MH  - Transcription Factor CHOP/metabolism
MH  - Transcription, Genetic
MH  - ets-Domain Protein Elk-1/metabolism
MH  - ras Proteins/*metabolism
PMC - PMC3249076
EDAT- 2011/11/09 06:00
MHDA- 2012/05/09 06:00
PMCR- 2013/01/02
CRDT- 2011/11/09 06:00
PHST- 2011/11/09 06:00 [entrez]
PHST- 2011/11/09 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
PHST- 2013/01/02 00:00 [pmc-release]
AID - S0021-9258(20)53510-2 [pii]
AID - M111.304006 [pii]
AID - 10.1074/jbc.M111.304006 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Jan 2;287(1):257-267. doi: 10.1074/jbc.M111.304006. Epub 2011 
      Nov 7.