PMID- 33586867
OWN - NLM
STAT- MEDLINE
DCOM- 20210531
LR  - 20220408
IS  - 1469-3178 (Electronic)
IS  - 1469-221X (Print)
IS  - 1469-221X (Linking)
VI  - 22
IP  - 4
DP  - 2021 Apr 7
TI  - EDC3 phosphorylation regulates growth and invasion through controlling P-body 
      formation and dynamics.
PG  - e50835
LID - 10.15252/embr.202050835 [doi]
LID - e50835
AB  - Regulation of mRNA stability and translation plays a critical role in determining 
      protein abundance within cells. Processing bodies (P-bodies) are critical 
      regulators of these processes. Here, we report that the Pim1 and 3 protein 
      kinases bind to the P-body protein enhancer of mRNA decapping 3 (EDC3) and 
      phosphorylate EDC3 on serine (S)161, thereby modifying P-body assembly. EDC3 
      phosphorylation is highly elevated in many tumor types, is reduced upon treatment 
      of cells with kinase inhibitors, and blocks the localization of EDC3 to P-bodies. 
      Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased 
      growth, migration, and invasion in tissue culture and in xenograft models. 
      Consistent with these phenotypic changes, the expression of integrin beta1 and alpha6 
      mRNA and protein is reduced in these mutated cells. These results demonstrate 
      that EDC3 phosphorylation regulates multiple cancer-relevant functions and 
      suggest that modulation of P-body activity may represent a new paradigm for 
      cancer treatment.
CI  - (c) 2021 The Authors.
FAU - Bearss, Jeremiah J
AU  - Bearss JJ
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
FAU - Padi, Sathish Kr
AU  - Padi SK
AUID- ORCID: 0000-0002-5526-4287
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Molecular Biology and Biophysics, UConn Health Center, Farmington, 
      CT, USA.
FAU - Singh, Neha
AU  - Singh N
AUID- ORCID: 0000-0001-9137-1103
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
FAU - Cardo-Vila, Marina
AU  - Cardo-Vila M
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Otolaryngology-Head and Neck Surgery, University of Arizona, 
      Tucson, AZ, USA.
FAU - Song, Jin H
AU  - Song JH
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, 
      USA.
FAU - Mouneimne, Ghassan
AU  - Mouneimne G
AD  - Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, 
      USA.
FAU - Fernandes, Nikita
AU  - Fernandes N
AD  - Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, 
      USA.
FAU - Li, Yang
AU  - Li Y
AD  - Department of Molecular Biology and Biophysics, UConn Health Center, Farmington, 
      CT, USA.
AD  - Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
FAU - Harter, Matthew R
AU  - Harter MR
AD  - Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
FAU - Gard, Jaime Mc
AU  - Gard JM
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
FAU - Cress, Anne E
AU  - Cress AE
AUID- ORCID: 0000-0001-6194-0061
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, 
      USA.
FAU - Peti, Wolfgang
AU  - Peti W
AD  - Department of Molecular Biology and Biophysics, UConn Health Center, Farmington, 
      CT, USA.
AD  - Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
FAU - Nelson, Andrew Dl
AU  - Nelson AD
AD  - Boyce Thompson Institute, Cornell University, Ithaca, NY, USA.
FAU - Buchan, J Ross
AU  - Buchan JR
AD  - Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, 
      USA.
FAU - Kraft, Andrew S
AU  - Kraft AS
AUID- ORCID: 0000-0003-3417-4845
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Medicine, University of Arizona, Tucson, AZ, USA.
FAU - Okumura, Koichi
AU  - Okumura K
AUID- ORCID: 0000-0002-6170-9342
AD  - University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
AD  - Department of Physiology, University of Arizona, Tucson, AZ, USA.
LA  - eng
GR  - R21 CA241010/CA/NCI NIH HHS/United States
GR  - T32 CA 9213-40/CA/NCI NIH HHS/United States
GR  - R01NS091336/NS/NINDS NIH HHS/United States
GR  - R01 NS091336/NS/NINDS NIH HHS/United States
GR  - R01 GM114564/GM/NIGMS NIH HHS/United States
GR  - T32 CA009213/CA/NCI NIH HHS/United States
GR  - R01 CA196885/CA/NCI NIH HHS/United States
GR  - R21CA241010-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210215
PL  - England
TA  - EMBO Rep
JT  - EMBO reports
JID - 100963049
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Mutation
MH  - Phosphorylation
MH  - *RNA Stability
MH  - RNA, Messenger/metabolism
PMC - PMC8025014
OTO - NOTNLM
OT  - P-bodies
OT  - cancers
OT  - kinases
OT  - mRNA processing
OT  - phosphorylation
COIS- The authors declare that they have no conflict of interest.
EDAT- 2021/02/16 06:00
MHDA- 2021/06/01 06:00
PMCR- 2022/04/07
CRDT- 2021/02/15 08:47
PHST- 2020/12/20 00:00 [revised]
PHST- 2020/05/07 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/02/16 06:00 [pubmed]
PHST- 2021/06/01 06:00 [medline]
PHST- 2021/02/15 08:47 [entrez]
PHST- 2022/04/07 00:00 [pmc-release]
AID - EMBR202050835 [pii]
AID - 10.15252/embr.202050835 [doi]
PST - ppublish
SO  - EMBO Rep. 2021 Apr 7;22(4):e50835. doi: 10.15252/embr.202050835. Epub 2021 Feb 
      15.