PMID- 10348343
OWN - NLM
STAT- MEDLINE
DCOM- 19990616
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 17
DP  - 1999 Apr 29
TI  - The double-stranded RNA activated protein kinase PKR physically associates with
      the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in
      vitro.
PG  - 2690-702
AB  - The tumor suppressor p53 is a multifunctional protein that plays a critical role 
      in modulating cellular responses upon DNA damage or other stresses. These
      functions of p53 are regulated both by protein-protein interactions and
      phosphorylation. The double-stranded RNA activated protein kinase PKR is a
      serine/threonine kinase that modulates protein synthesis through the
      phosphorylation of translation initiation factor eIF-2alpha. PKR is an interferon
      (IFN)-inducible protein that is thought to mediate the anti-viral and
      anti-proliferative effects of IFN via its capacity to inhibit protein synthesis. 
      Here we report that PKR physically associates with p53. The interaction of PKR
      with p53 is enhanced by IFNs and upon conditions that p53 acquires a wild type
      conformation. PKR/p53 complex formation in vitro requires the N-terminal
      regulatory domain of PKR and the last 30 amino acids of the C-terminus of human
      p53. In addition, p53 may function as a substrate of PKR since phosphorylation of
      human p53 on serine392 is induced by activated PKR in vitro. These novel findings
      raise the possibility of a functional interaction between PKR and p53 in vivo,
      which may account, at least in part, for the ability of each protein to regulate 
      gene expression at both the transcriptional and the translational levels.
FAU - Cuddihy, A R
AU  - Cuddihy AR
AD  - Department of Oncology, McGill University, Montreal, Quebec, Canada.
FAU - Wong, A H
AU  - Wong AH
FAU - Tam, N W
AU  - Tam NW
FAU - Li, S
AU  - Li S
FAU - Koromilas, A E
AU  - Koromilas AE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Humans
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Structure, Tertiary
MH  - RNA, Double-Stranded/*genetics
MH  - Serine/*metabolism
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - eIF-2 Kinase/*metabolism
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
AID - 10.1038/sj.onc.1202620 [doi]
PST - ppublish
SO  - Oncogene. 1999 Apr 29;18(17):2690-702. doi: 10.1038/sj.onc.1202620.