PMID- 21499441
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211020
IS  - 1938-1247 (Print)
IS  - 1938-1247 (Electronic)
IS  - 1938-1247 (Linking)
VI  - 2
IP  - 5
DP  - 2010
TI  - Over Expression of Nucleophosmin and Nucleolin Contributes to the Suboptimal 
      Activation of a G2/M Checkpoint in Ataxia Telangiectasia Fibroblasts.
PG  - 179-189
AB  - Ataxia Telangiectasia (AT) cells exhibit suboptimal activation of 
      radiation-induced cell cycle checkpoints despite having a wild type p53 genotype. 
      Reducing or eliminating this delay could restore p53 function and reinstate 
      normal cellular response to genotoxic stress. Here we show that the levels of 
      Nuclephosmin (NPM), NPM phosphorylated at Serine 125, p53, p53 phosphorylated at 
      Serine 15 and Serine 392 and the levels of Nucleolin (NCL) are high in AT 
      fibroblasts compared to normal cells. Transfection of a functional ATM into AT 
      fibroblasts reduced p53, phospo-p53, phospho-NPM and NCL levels to wild type 
      fibroblasts levels. Our data indicate that ATM regulates phospho-NPM and NCL 
      indirectly through the Protein Phosphatase 1 (PP1). Both, NPM and NCL interact 
      with p53 and hinder its phosphorylation at Serine 15 in response to bleomycin. 
      Moreover, NPM and NCL are phosphorylated by several of the same kinases targeting 
      p53 and could potentially compete with p53 for phosphorylation in AT cells. In 
      addition, our data indicate that down regulation of NCL and to a lesser extent 
      NPM increase the number of AT cells arrested in G2/M in response to bleomycin. 
      Together this data indicate that the lack of PP1 activation in AT cells result in 
      increased NPM and NCL protein levels which prevents p53 phosphorylation in 
      response to bleomycin and contributes to a defective G2/M checkpoint.
FAU - Nalabothula, Narasimharao
AU  - Nalabothula N
AD  - Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, 
      Maryland.
FAU - Chakravarty, Devulapalli
AU  - Chakravarty D
FAU - Pierce, Adam
AU  - Pierce A
FAU - Carrier, France
AU  - Carrier F
LA  - eng
GR  - R01 CA116491/CA/NCI NIH HHS/United States
GR  - R01 CA116491-03/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Mol Cell Pharmacol
JT  - Molecular and cellular pharmacology
JID - 101516660
PMC - PMC3076699
MID - NIHMS262248
COIS- Conflicts of Interest No potential conflicts of interest to disclose.
EDAT- 2010/01/01 00:00
MHDA- 2010/01/01 00:01
PMCR- 2011/04/14
CRDT- 2011/04/19 06:00
PHST- 2011/04/19 06:00 [entrez]
PHST- 2010/01/01 00:00 [pubmed]
PHST- 2010/01/01 00:01 [medline]
PHST- 2011/04/14 00:00 [pmc-release]
PST - ppublish
SO  - Mol Cell Pharmacol. 2010;2(5):179-189.