PMID- 10551811
OWN - NLM
STAT- MEDLINE
DCOM- 20000103
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 46
DP  - 1999 Nov 12
TI  - Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun
      N-terminal kinase.
PG  - 32580-7
AB  - The expression of c-myc promotes cell proliferation and also sensitizes cells to 
      various extracellular apoptotic stimuli. However, signal pathways regulating the 
      function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase
      (JNK) is activated by various apoptotic stimuli, but neither the target
      molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis.
      Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at
      Ser-62 and Ser-71 as confirmed with phospho-c-Myc-specific antibodies.
      Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent
      apoptosis, but not mutated c-Myc (S62A/S71A)-dependent apoptosis triggered by UV 
      irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not
      sensitized like wild type c-Myc-expressing NIH3T3 cells to JNK-activating
      apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK
      pathway is selectively involved in the c-Myc-mediated apoptosis and that the
      apoptotic function of c-Myc is directly regulated by JNK pathway through
      phosphorylation at Ser-62 and Ser-71.
FAU - Noguchi, K
AU  - Noguchi K
AD  - Biophysics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji,
      Chuo-ku, Tokyo 104-0045, Japan.
FAU - Kitanaka, C
AU  - Kitanaka C
FAU - Yamana, H
AU  - Yamana H
FAU - Kokubu, A
AU  - Kokubu A
FAU - Mochizuki, T
AU  - Mochizuki T
FAU - Kuchino, Y
AU  - Kuchino Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Apoptosis
MH  - Gene Expression Regulation
MH  - HeLa Cells
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis
MH  - Paclitaxel/pharmacology
MH  - Phosphorylation
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-myc/genetics/*metabolism
MH  - Recombinant Fusion Proteins
MH  - Signal Transduction
MH  - Ultraviolet Rays
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
AID - 10.1074/jbc.274.46.32580 [doi]
AID - S0021-9258(17)46550-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 12;274(46):32580-7. doi: 10.1074/jbc.274.46.32580.