PMID- 27402756
OWN - NLM
STAT- MEDLINE
DCOM- 20180205
LR  - 20201209
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 113
IP  - 30
DP  - 2016 Jul 26
TI  - Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 
      Ser83 may contribute to cell transformation.
PG  - 8466-71
LID - 10.1073/pnas.1607768113 [doi]
AB  - Mammalian target of rapamycin (mTOR)-directed eukaryotic translation initiation 
      factor 4E-binding protein 1 (4E-BP1) phosphorylation promotes cap-dependent 
      translation and tumorigenesis. During mitosis, cyclin-dependent kinase 1 (CDK1) 
      substitutes for mTOR and fully phosphorylates 4E-BP1 at canonical sites (T37, 
      T46, S65, and T70) and the noncanonical S83 site, resulting in a mitosis-specific 
      hyperphosphorylated delta isoform. Colocalization studies with a phospho-S83 specific 
      antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes 
      during prophase, peaks at metaphase, and decreases through telophase. Although 
      S83 phosphorylation of 4E-BP1 does not affect general cap-dependent translation, 
      expression of an alanine substitution mutant 4E-BP1.S83A partially reverses 
      rodent cell transformation induced by Merkel cell polyomavirus small T antigen 
      viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these 
      findings suggest that mitotic CDK1-directed phosphorylation of delta-4E-BP1 may yield 
      a gain of function, distinct from translation regulation, that may be important 
      in tumorigenesis and mitotic centrosome function.
FAU - Velasquez, Celestino
AU  - Velasquez C
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213;
FAU - Cheng, Erdong
AU  - Cheng E
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213;
FAU - Shuda, Masahiro
AU  - Shuda M
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213;
FAU - Lee-Oesterreich, Paula J
AU  - Lee-Oesterreich PJ
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213;
FAU - Pogge von Strandmann, Lisa
AU  - Pogge von Strandmann L
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213;
FAU - Gritsenko, Marina A
AU  - Gritsenko MA
AD  - Biological Sciences Division/Biological Systems Analysis & Mass Spectrometry, 
      Pacific Northwest National Laboratory, Richland, WA 99352.
FAU - Jacobs, Jon M
AU  - Jacobs JM
AD  - Biological Sciences Division/Biological Systems Analysis & Mass Spectrometry, 
      Pacific Northwest National Laboratory, Richland, WA 99352.
FAU - Moore, Patrick S
AU  - Moore PS
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213; yc70@pitt.edu psm9@pitt.edu.
FAU - Chang, Yuan
AU  - Chang Y
AD  - Cancer Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, 
      PA 15213; yc70@pitt.edu psm9@pitt.edu.
LA  - eng
GR  - P41 GM103493/GM/NIGMS NIH HHS/United States
GR  - R01 CA170354/CA/NCI NIH HHS/United States
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - R01 CA136363/CA/NCI NIH HHS/United States
GR  - R01 CA136806/CA/NCI NIH HHS/United States
GR  - R35 CA197463/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160711
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 2.7.11.22 (CDK1 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - CDC2 Protein Kinase/genetics/*metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - Centrosome/metabolism
MH  - HCT116 Cells
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Humans
MH  - Mitosis/genetics
MH  - Mutation
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - RNA, Messenger/genetics
MH  - Serine/genetics/*metabolism
PMC - PMC4968757
OTO - NOTNLM
OT  - 4E-BP
OT  - Merkel cell polyomavirus
OT  - cap-dependent translation
OT  - cyclin-dependent kinase 1
OT  - mitosis
COIS- The authors declare no conflict of interest.
EDAT- 2016/07/13 06:00
MHDA- 2018/02/06 06:00
PMCR- 2016/07/11
CRDT- 2016/07/13 06:00
PHST- 2016/07/13 06:00 [entrez]
PHST- 2016/07/13 06:00 [pubmed]
PHST- 2018/02/06 06:00 [medline]
PHST- 2016/07/11 00:00 [pmc-release]
AID - 1607768113 [pii]
AID - 201607768 [pii]
AID - 10.1073/pnas.1607768113 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):8466-71. doi: 
      10.1073/pnas.1607768113. Epub 2016 Jul 11.