PMID- 30091641
OWN - NLM
STAT- MEDLINE
DCOM- 20190506
LR  - 20231213
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 29
IP  - 20
DP  - 2018 Oct 1
TI  - WDR62 mediates TNFalpha-dependent JNK activation via TRAF2-MLK3 axis.
PG  - 2470-2480
LID - 10.1091/mbc.E17-08-0504 [doi]
AB  - The mitogen-activated protein kinases (MAPKs) regulate a variety of cellular 
      processes. The three main MAPK cascades are the extracellular signal-regulated 
      kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinases. A typical MAPK 
      cascade is composed of MAP3K-MAP2K-MAPK kinases that are held by scaffold 
      proteins. Scaffolds function to assemble the protein tier and contribute to the 
      specificity and efficacy of signal transmission. WD repeat domain 62 (WDR62) is a 
      JNK scaffold protein, interacting with JNK, MKK7, and several MAP3Ks. The loss of 
      WDR62 in human leads to microcephaly and pachygyria. Yet the role of WDR62 in 
      cellular function is not fully studied. We used the CRISPR/Cas9 and short hairpin 
      RNA approaches to establish a human breast cancer cell line MDA-MB-231 with WDR62 
      loss of function and studied the consequence to JNK signaling. In growing cells, 
      WDR62 is responsible for the basal expression of c-Jun. In stressed cells, WDR62 
      specifically mediates TNFalpha-dependent JNK activation through the association with 
      both the adaptor protein, TNF receptor-associated factor 2 (TRAF2), and the MAP3K 
      protein, mixed lineage kinase 3. TNFalpha-dependent JNK activation is mediated by 
      WDR62 in HCT116 and HeLa cell lines as well. MDA-MB-231 WDR62-knockout cells 
      display increased resistance to TNFalpha-induced cell death. Collectively, WDR62 
      coordinates the TNFalpha receptor signaling pathway to JNK activation through 
      association with multiple kinases and the adaptor protein TRAF2.
FAU - Prinz, Elad
AU  - Prinz E
AD  - Department of Cell Biology and Cancer Science, B. Rappaport Faculty of Medicine, 
      Technion-Israel Institute of Technology, Haifa 31096, Israel.
FAU - Aviram, Sharon
AU  - Aviram S
AD  - Department of Cell Biology and Cancer Science, B. Rappaport Faculty of Medicine, 
      Technion-Israel Institute of Technology, Haifa 31096, Israel.
FAU - Aronheim, Ami
AU  - Aronheim A
AD  - Department of Cell Biology and Cancer Science, B. Rappaport Faculty of Medicine, 
      Technion-Israel Institute of Technology, Haifa 31096, Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180809
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (WDR62 protein, human)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Base Sequence
MH  - Cell Cycle Proteins
MH  - Cell Line, Tumor
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - MAP Kinase Kinase Kinases/*metabolism
MH  - Models, Biological
MH  - Nerve Tissue Proteins/*metabolism
MH  - Protein Binding/drug effects
MH  - *Signal Transduction/drug effects
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Mitogen-Activated Protein Kinase Kinase Kinase 11
PMC - PMC6233063
EDAT- 2018/08/10 06:00
MHDA- 2019/05/07 06:00
PMCR- 2018/12/16
CRDT- 2018/08/10 06:00
PHST- 2018/08/10 06:00 [pubmed]
PHST- 2019/05/07 06:00 [medline]
PHST- 2018/08/10 06:00 [entrez]
PHST- 2018/12/16 00:00 [pmc-release]
AID - E17-08-0504 [pii]
AID - 10.1091/mbc.E17-08-0504 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2018 Oct 1;29(20):2470-2480. doi: 10.1091/mbc.E17-08-0504. Epub 
      2018 Aug 9.