PMID- 9343408
OWN - NLM
STAT- MEDLINE
DCOM- 19971121
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 17
IP  - 11
DP  - 1997 Nov
TI  - Identification of a viral kinase that phosphorylates specific E2Fs and pocket 
      proteins.
PG  - 6459-64
AB  - The transcription factor E2F and its regulation by pRB and related pocket 
      proteins are central to cell cycle control in higher eukaryotes. Much of our 
      knowledge of this regulation has come from studies using immediate-early proteins 
      of DNA tumor viruses. Previously, we reported that the 72-kDa immediate-early 
      region 1 gene product of the human cytomegalovirus, IE72, transactivates the 
      dihydrofolate reductase promoter through the E2F site and that it physically 
      interacts with E2F1 (M. J. Margolis, S. Pajovic, E. L. Wong, M. Wade, R. Jupp, J. 
      A. Nelson, and J. C. Azizkhan, J. Virol. 69:7759-7767, 1995). In this study, we 
      further characterized the mechanism by which IE72 modulates E2F-dependent 
      transcription. In vitro phosphorylation reactions using gel-purified bacterially 
      expressed proteins revealed that IE72 is a kinase that autophosphorylates and 
      phosphorylates E2F1, -2, and -3 (but not E2F4 or -5) and the RB-related pocket 
      proteins p130 and p107 (but not pRB). The region of IE72 spanning amino acids 173 
      to 197 shows a high level of homology to the ATP binding sites in over 500 
      kinases. The kinase-negative protein IE72deltaATP, from which this region has 
      been deleted, cannot activate E2F-dependent transcription. The kinase activity of 
      IE72 is also required for its ability to reduce the association of E2F4 with p107 
      and p130. Taken together, these data suggest that the kinase activity of IE72 is 
      required for E2F-dependent transcriptional activation and that this is likely to 
      result from phosphorylation of specific members of the E2F and pocket protein 
      families by IE72.
FAU - Pajovic, S
AU  - Pajovic S
AD  - Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, 
      New York 14263, USA.
FAU - Wong, E L
AU  - Wong EL
FAU - Black, A R
AU  - Black AR
FAU - Azizkhan, J C
AU  - Azizkhan JC
LA  - eng
GR  - CA71019/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (IE1 protein, cytomegalovirus)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (Retinoblastoma-Like Protein p130)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Carrier Proteins
MH  - *Cell Cycle Proteins
MH  - Cytomegalovirus/*enzymology
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - E2F1 Transcription Factor
MH  - Immediate-Early Proteins/*metabolism
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/*metabolism
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - *Proteins
MH  - Retinoblastoma-Binding Protein 1
MH  - Retinoblastoma-Like Protein p130
MH  - Substrate Specificity
MH  - Transcription Factor DP1
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - *Viral Proteins
PMC - PMC232498
EDAT- 1997/10/29 00:00
MHDA- 1997/10/29 00:01
PMCR- 1997/11/01
CRDT- 1997/10/29 00:00
PHST- 1997/10/29 00:00 [pubmed]
PHST- 1997/10/29 00:01 [medline]
PHST- 1997/10/29 00:00 [entrez]
PHST- 1997/11/01 00:00 [pmc-release]
AID - 10.1128/MCB.17.11.6459 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1997 Nov;17(11):6459-64. doi: 10.1128/MCB.17.11.6459.