PMID- 25460043
OWN - NLM
STAT- MEDLINE
DCOM- 20150825
LR  - 20240210
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 27
IP  - 2
DP  - 2015 Feb
TI  - Regulation of DNA damage responses and cell cycle progression by hMOB2.
PG  - 326-39
LID - S0898-6568(14)00370-2 [pii]
LID - 10.1016/j.cellsig.2014.11.016 [doi]
AB  - Mps one binder proteins (MOBs) are conserved regulators of essential signalling 
      pathways. Biochemically, human MOB2 (hMOB2) can inhibit NDR kinases by competing 
      with hMOB1 for binding to NDRs. However, biological roles of hMOB2 have remained 
      enigmatic. Here, we describe novel functions of hMOB2 in the DNA damage response 
      (DDR) and cell cycle regulation. hMOB2 promotes DDR signalling, cell survival and 
      cell cycle arrest after exogenously induced DNA damage. Under normal growth 
      conditions in the absence of exogenously induced DNA damage hMOB2 plays a role in 
      preventing the accumulation of endogenous DNA damage and a subsequent 
      p53/p21-dependent G1/S cell cycle arrest. Unexpectedly, these molecular and 
      cellular phenotypes are not observed upon NDR manipulations, indicating that 
      hMOB2 performs these functions independent of NDR signalling. Thus, to gain 
      mechanistic insight, we screened for novel binding partners of hMOB2, revealing 
      that hMOB2 interacts with RAD50, facilitating the recruitment of the 
      MRE11-RAD50-NBS1 (MRN) DNA damage sensor complex and activated ATM to DNA damaged 
      chromatin. Taken together, we conclude that hMOB2 supports the DDR and cell cycle 
      progression.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Gomez, Valenti
AU  - Gomez V
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom.
FAU - Gundogdu, Ramazan
AU  - Gundogdu R
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom.
FAU - Gomez, Marta
AU  - Gomez M
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom.
FAU - Hoa, Lily
AU  - Hoa L
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom.
FAU - Panchal, Neelam
AU  - Panchal N
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom.
FAU - O'Driscoll, Mark
AU  - O'Driscoll M
AD  - Genome Damage and Stability Centre, University of Sussex, BN1 9RH, Brighton, 
      United Kingdom.
FAU - Hergovich, Alexander
AU  - Hergovich A
AD  - UCL Cancer Institute, University College London, WC1E 6BT, London, United 
      Kingdom. Electronic address: a.hergovich@ucl.ac.uk.
LA  - eng
GR  - 090090/Z/09/Z/WT_/Wellcome Trust/United Kingdom
GR  - 11-0634/AICR_/Worldwide Cancer Research/United Kingdom
GR  - (BB/I021248/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - 090090/WT_/Wellcome Trust/United Kingdom
GR  - 15394/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141121
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (MOB2 protein, human)
RN  - 0 (NBN protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (structural maintenance of chromosome protein 1)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Ataxia Telangiectasia Mutated Proteins/metabolism
MH  - COS Cells
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Line, Tumor
MH  - Chlorocebus aethiops
MH  - Chromosomal Proteins, Non-Histone/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - *DNA Damage
MH  - Doxorubicin/pharmacology
MH  - G1 Phase Cell Cycle Checkpoints/drug effects/radiation effects
MH  - Humans
MH  - Nerve Tissue Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Nuclear Proteins/metabolism
MH  - Phosphorylation/drug effects/radiation effects
MH  - RNA, Small Interfering/metabolism
MH  - Radiation, Ionizing
MH  - S Phase Cell Cycle Checkpoints/drug effects/radiation effects
MH  - Signal Transduction/drug effects/radiation effects
MH  - Tumor Suppressor Protein p53/antagonists & inhibitors/genetics/metabolism
PMC - PMC4276419
MID - EMS61424
OID - NLM: EMS61424
OTO - NOTNLM
OT  - Cell cycle checkpoint activation
OT  - Cell cycle progression
OT  - DNA damage response signalling
OT  - MRE11-RAD50-NBS1 protein complex
OT  - Mps one binder 2
OT  - p53 tumour suppressor protein
EDAT- 2014/12/03 06:00
MHDA- 2015/08/26 06:00
PMCR- 2015/02/01
CRDT- 2014/12/03 06:00
PHST- 2014/09/17 00:00 [received]
PHST- 2014/11/03 00:00 [revised]
PHST- 2014/11/14 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/08/26 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - S0898-6568(14)00370-2 [pii]
AID - 10.1016/j.cellsig.2014.11.016 [doi]
PST - ppublish
SO  - Cell Signal. 2015 Feb;27(2):326-39. doi: 10.1016/j.cellsig.2014.11.016. Epub 2014 
      Nov 21.