PMID- 37145994
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20231201
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 5
DP  - 2023
TI  - Mitotic CDK1 and 4E-BP1 I: Loss of 4E-BP1 serine 82 phosphorylation promotes 
      proliferative polycystic disease and lymphoma in aged or sublethally irradiated 
      mice.
PG  - e0282722
LID - 10.1371/journal.pone.0282722 [doi]
LID - e0282722
AB  - 4E-BP1 is a tumor suppressor regulating cap-dependent translation that is in turn 
      controlled by mechanistic target of rapamycin (mTOR) or cyclin-dependent kinase 1 
      (CDK1) phosphorylation. 4E-BP1 serine 82 (S82) is phosphorylated by CDK1, but not 
      mTOR, and the consequences of this mitosis-specific phosphorylation are unknown. 
      Knock-in mice were generated with a single 4E-BP1 S82 alanine (S82A) substitution 
      leaving other phosphorylation sites intact. S82A mice were fertile and exhibited 
      no gross developmental or behavioral abnormalities, but the homozygotes developed 
      diffuse and severe polycystic liver and kidney disease with aging, and lymphoid 
      malignancies after irradiation. Sublethal irradiation caused immature T-cell 
      lymphoma only in S82A mice while S82A homozygous mice have normal T-cell 
      hematopoiesis before irradiation. Whole genome sequencing identified PTEN 
      mutations in S82A lymphoma and impaired PTEN expression was verified in S82A 
      lymphomas derived cell lines. Our study suggests that the absence of 4E-BP1S82 
      phosphorylation, a subtle change in 4E-BP1 phosphorylation, might predispose to 
      polycystic proliferative disease and lymphoma under certain stressful 
      circumstances, such as aging and irradiation.
CI  - Copyright: (c) 2023 Sun et al. This is an open access article distributed under the 
      terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Sun, Rui
AU  - Sun R
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Guo, Siying
AU  - Guo S
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Shuda, Yoko
AU  - Shuda Y
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Chakka, Anish B
AU  - Chakka AB
AD  - Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, 
      Pennsylvania, United States of America.
FAU - Rigatti, Lora H
AU  - Rigatti LH
AD  - Division of Laboratory Animal Resources, University of Pittsburgh Cancer 
      Institute, Pittsburgh, Pennsylvania, United States of America.
FAU - Zhao, Guangyi
AU  - Zhao G
AD  - Department of Pathology, University of Pittsburgh School of Medicine, UPMC 
      Hillman Cancer Center, Pittsburgh, Pennsylvania, United States of America.
FAU - Ali, Mohammed A E
AU  - Ali MAE
AD  - Department of Pathology, NYU Grossman School of Medicine, Perlmutter Cancer 
      Center, New York, New York, United States of America.
FAU - Park, Christopher Y
AU  - Park CY
AD  - Department of Pathology, NYU Grossman School of Medicine, Perlmutter Cancer 
      Center, New York, New York, United States of America.
FAU - Chandran, Uma
AU  - Chandran U
AD  - Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, 
      Pennsylvania, United States of America.
FAU - Yu, Jian
AU  - Yu J
AD  - Department of Pathology, University of Pittsburgh School of Medicine, UPMC 
      Hillman Cancer Center, Pittsburgh, Pennsylvania, United States of America.
FAU - Bakkenist, Christopher J
AU  - Bakkenist CJ
AD  - Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, United 
      States of America.
FAU - Shuda, Masahiro
AU  - Shuda M
AUID- ORCID: 0000-0003-0595-2572
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Moore, Patrick S
AU  - Moore PS
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
FAU - Chang, Yuan
AU  - Chang Y
AUID- ORCID: 0000-0003-1125-4041
AD  - Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 
      United States of America.
AD  - Department of Pathology, University of Pittsburgh School of Medicine, UPMC 
      Hillman Cancer Center, Pittsburgh, Pennsylvania, United States of America.
LA  - eng
GR  - R01 CA215481/CA/NCI NIH HHS/United States
GR  - P50 CA121973/CA/NCI NIH HHS/United States
GR  - R01 CA260900/CA/NCI NIH HHS/United States
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - R01 CA232604/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 - 20230505
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - 452VLY9402 (Serine)
RN  - 0 (Phosphoproteins)
RN  - 0 (Cell Cycle Proteins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *CDC2 Protein Kinase/genetics/metabolism
MH  - Phosphorylation
MH  - Serine/metabolism
MH  - Phosphoproteins/metabolism
MH  - Cell Cycle Proteins/genetics/metabolism
MH  - *Lymphoma/genetics
PMC - PMC10162543
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/05/05 18:42
MHDA- 2023/05/08 10:17
PMCR- 2023/05/05
CRDT- 2023/05/05 13:23
PHST- 2022/10/20 00:00 [received]
PHST- 2023/02/21 00:00 [accepted]
PHST- 2023/05/08 10:17 [medline]
PHST- 2023/05/05 18:42 [pubmed]
PHST- 2023/05/05 13:23 [entrez]
PHST- 2023/05/05 00:00 [pmc-release]
AID - PONE-D-22-29036 [pii]
AID - 10.1371/journal.pone.0282722 [doi]
PST - epublish
SO  - PLoS One. 2023 May 5;18(5):e0282722. doi: 10.1371/journal.pone.0282722. 
      eCollection 2023.