PMID- 10023679
OWN - NLM
STAT- MEDLINE
DCOM- 19990223
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 4
DP  - 1999 Jan 28
TI  - Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox
      regulation of AP-1.
PG  - 1033-40
AB  - The DNA repair protein apurinic endonuclease (APE/Ref-1) exerts several
      physiological functions such as cleavage of apurinic/apyrimidinic sites and redox
      regulation of the transcription factor AP-1, whose activation is part of the
      cellular response to DNA damaging treatments. Here we demonstrate that APE/Ref-1 
      is phosphorylated by casein kinase II (CKII). This was shown for both the
      recombinant APE/Ref-1 protein (Km=0.55 mM) and for APE/Ref-1 expressed in COS
      cells. Phosphorylation of APE/Ref-1 did not alter the repair activity of the
      enzyme, whereas it stimulated its redox capability towards AP-1, thus promoting
      DNA binding activity of AP-1. Inhibition of CKII mediated phosphorylation of
      APE/Ref-1 blocked mutagen-stimulated increase in AP-1 binding. It also abrogated 
      the induction of c-Jun protein and rendered cells more sensitive to induced DNA
      damage. Thus, phosphorylation of APE/Ref-1 appears to be involved in regulating
      the different physiological activities of the enzyme. CKII mediated
      phosphorylation of APE/Ref-1 and concomitant increase in AP-1 binding activity
      appears to be a novel mechanism of cellular stress response, forcing
      transcription of AP-1 target gene(s) the product(s) of which may exert protective
      function.
FAU - Fritz, G
AU  - Fritz G
AD  - Division of Applied Toxicology, Institute of Toxicology, University of Mainz,
      Germany.
FAU - Kaina, B
AU  - Kaina B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Mutagens)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Transcription Factor AP-1)
RN  - AT5C31J09G (Methyl Methanesulfonate)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 4.2.- (Carbon-Oxygen Lyases)
RN  - EC 4.2.99.18 (APEX1 protein, human)
RN  - EC 4.2.99.18 (DNA-(Apurinic or Apyrimidinic Site) Lyase)
SB  - IM
MH  - Animals
MH  - CHO Cells/drug effects
MH  - COS Cells/drug effects
MH  - Carbon-Oxygen Lyases/genetics/*metabolism/physiology
MH  - Casein Kinase II
MH  - Cricetinae
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - DNA Damage
MH  - *DNA Repair
MH  - *DNA-(Apurinic or Apyrimidinic Site) Lyase
MH  - HeLa Cells/drug effects
MH  - Humans
MH  - Methyl Methanesulfonate/pharmacology
MH  - Mutagens/pharmacology
MH  - Oxidation-Reduction
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - Substrate Specificity
MH  - Transcription Factor AP-1/*metabolism
MH  - Transfection
EDAT- 1999/02/19 00:00
MHDA- 1999/02/19 00:01
CRDT- 1999/02/19 00:00
PHST- 1999/02/19 00:00 [pubmed]
PHST- 1999/02/19 00:01 [medline]
PHST- 1999/02/19 00:00 [entrez]
AID - 10.1038/sj.onc.1202394 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jan 28;18(4):1033-40. doi: 10.1038/sj.onc.1202394.