PMID- 19064990
OWN - NLM
STAT- MEDLINE
DCOM- 20090331
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 7
DP  - 2009 Feb 13
TI  - ATM-mediated transcriptional elevation of prion in response to copper-induced 
      oxidative stress.
PG  - 4582-93
LID - 10.1074/jbc.M808410200 [doi]
AB  - Increasing evidence suggests that the cellular prion protein (PrP(C)) plays a 
      protective role in response to oxidative stress, but the molecular mechanism is 
      unclear. Here, we demonstrate that murine neuro-2a and human HeLa cells rapidly 
      respond to an increase of intracellular copper concentration by up-regulating 
      ataxia-telangiectasia mutated (ATM)-mediated transcription of PrP(C). Copper 
      stimulation activates ATM by phosphorylation at Ser-1981, which leads to 
      phosphorylation of p53 at Ser-15 and the initiation of the mitogen-activated 
      protein kinase kinase/extracellular-related kinases/extracellular-related kinases 
      (MEK/ERK)/Sp1 pathway. As results, Sp1 and p53 bind to the PrP promoter, leading 
      to increase PrP(C) expression. Elevated PrP(C) correlates with reduction of 
      intracellular copper concentration and suppression of Cu(II)-induced accumulation 
      of reactive oxygen species and cell death. Depletion of PrP(C), ATM, p53, and/or 
      Sp1 further demonstrates that ATM is a key regulatory protein to promote 
      activation of p53 and Sp1 leading to PrP(C) elevation, which is required to 
      reduce Cu(II) toxic effects and may play an important role in modulation of 
      intracellular copper concentration.
FAU - Qin, Kefeng
AU  - Qin K
AD  - Departments of Pathology and Microbiology-Immunology and Institute of Human 
      Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, 
      USA.
FAU - Zhao, Lili
AU  - Zhao L
FAU - Ash, Richard D
AU  - Ash RD
FAU - McDonough, William F
AU  - McDonough WF
FAU - Zhao, Richard Y
AU  - Zhao RY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081208
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (PrPC Proteins)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 789U1901C5 (Copper)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Atm protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins/*metabolism
MH  - Copper/metabolism/*pharmacology
MH  - DNA-Binding Proteins/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Regulation/*drug effects/physiology
MH  - HeLa Cells
MH  - Humans
MH  - Mice
MH  - Oxidative Stress/*drug effects/physiology
MH  - Phosphorylation/drug effects/physiology
MH  - PrPC Proteins/*biosynthesis
MH  - Promoter Regions, Genetic/physiology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Sp1 Transcription Factor/metabolism
MH  - Transcription, Genetic/*drug effects/physiology
MH  - Tumor Suppressor Protein p53/metabolism
MH  - Tumor Suppressor Proteins/*metabolism
EDAT- 2008/12/10 09:00
MHDA- 2009/04/01 09:00
CRDT- 2008/12/10 09:00
PHST- 2008/12/10 09:00 [pubmed]
PHST- 2009/04/01 09:00 [medline]
PHST- 2008/12/10 09:00 [entrez]
AID - S0021-9258(20)71061-6 [pii]
AID - 10.1074/jbc.M808410200 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Feb 13;284(7):4582-93. doi: 10.1074/jbc.M808410200. Epub 2008 
      Dec 8.