PMID- 27642049
OWN - NLM
STAT- MEDLINE
DCOM- 20170829
LR  - 20180628
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Linking)
VI  - 64
IP  - 1
DP  - 2016 Oct 6
TI  - The N-Terminal Phosphorylation of RB by p38 Bypasses Its Inactivation by CDKs and 
      Prevents Proliferation in Cancer Cells.
PG  - 25-36
LID - S1097-2765(16)30429-4 [pii]
LID - 10.1016/j.molcel.2016.08.015 [doi]
AB  - Control of the G1/S phase transition by the Retinoblastoma (RB) tumor suppressor 
      is critical for the proliferation of normal cells in tissues, and its 
      inactivation is one of the most fundamental events leading to cancer. 
      Cyclin-dependent kinase (CDK) phosphorylation inactivates RB to promote cell 
      cycle-regulated gene expression. Here we show that, upon stress, the p38 
      stress-activated protein kinase (SAPK) maximizes cell survival by downregulating 
      E2F gene expression through the targeting of RB. RB undergoes selective 
      phosphorylation by p38 in its N terminus; these phosphorylations render RB 
      insensitive to the inactivation by CDKs. p38 phosphorylation of RB increases its 
      affinity toward the E2F transcription factor, represses gene expression, and 
      delays cell-cycle progression. Remarkably, introduction of a RB phosphomimetic 
      mutant in cancer cells reduces colony formation and decreases their proliferative 
      and tumorigenic potential in mice.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Gubern, Albert
AU  - Gubern A
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Joaquin, Manel
AU  - Joaquin M
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Marques, Miriam
AU  - Marques M
AD  - Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National 
      Cancer Research Centre (CNIO), 28029 Madrid, Spain; Departament de Ciencies 
      Experimentals i de la Salut, UPF, 08003 Barcelona, Spain.
FAU - Maseres, Pedro
AU  - Maseres P
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Garcia-Garcia, Javier
AU  - Garcia-Garcia J
AD  - Structural Bioinformatics Group (GRIB), Departament de Ciencies Experimentals i 
      de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Amat, Ramon
AU  - Amat R
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Gonzalez-Nunez, Daniel
AU  - Gonzalez-Nunez D
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Oliva, Baldo
AU  - Oliva B
AD  - Structural Bioinformatics Group (GRIB), Departament de Ciencies Experimentals i 
      de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
FAU - Real, Francisco X
AU  - Real FX
AD  - Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National 
      Cancer Research Centre (CNIO), 28029 Madrid, Spain; Departament de Ciencies 
      Experimentals i de la Salut, UPF, 08003 Barcelona, Spain.
FAU - de Nadal, Eulalia
AU  - de Nadal E
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain. Electronic 
      address: eulalia.nadal@upf.edu.
FAU - Posas, Francesc
AU  - Posas F
AD  - Cell Signaling Research Group, Departament de Ciencies Experimentals i de la 
      Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain. Electronic 
      address: francesc.posas@upf.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160915
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (E2F Transcription Factors)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cyclin-Dependent Kinases/*genetics/metabolism
MH  - E2F Transcription Factors/*genetics/metabolism
MH  - Epithelial Cells/metabolism/pathology
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MAP Kinase Kinase 4/genetics/metabolism
MH  - Mice
MH  - Molecular Mimicry
MH  - Phosphorylation
MH  - Protein Interaction Domains and Motifs
MH  - Protein Structure, Secondary
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Retinoblastoma Protein/chemistry/*genetics/metabolism
MH  - Signal Transduction
MH  - Xenograft Model Antitumor Assays
MH  - p38 Mitogen-Activated Protein Kinases/*genetics/metabolism
EDAT- 2016/09/20 06:00
MHDA- 2017/08/30 06:00
CRDT- 2016/09/20 06:00
PHST- 2016/05/31 00:00 [received]
PHST- 2016/06/21 00:00 [revised]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/09/20 06:00 [pubmed]
PHST- 2017/08/30 06:00 [medline]
PHST- 2016/09/20 06:00 [entrez]
AID - S1097-2765(16)30429-4 [pii]
AID - 10.1016/j.molcel.2016.08.015 [doi]
PST - ppublish
SO  - Mol Cell. 2016 Oct 6;64(1):25-36. doi: 10.1016/j.molcel.2016.08.015. Epub 2016 
      Sep 15.