PMID- 9060648
OWN - NLM
STAT- MEDLINE
DCOM- 19970411
LR  - 20211203
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 71
IP  - 4
DP  - 1997 Apr
TI  - Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the 
      human papillomavirus type 16 E7 oncoprotein.
PG  - 2905-12
AB  - Cells expressing human papillomavirus type 16 (HPV-16) E7, similar to those which 
      express HPV-16 E6, are resistant to a p53-mediated G1 growth arrest. We examined 
      the p53-mediated DNA damage response pathway in E7-expressing cells to determine 
      the mechanism by which E7-containing cells continue to cycle. In response to DNA 
      damage, no dramatic difference was detected in G1- or S-phase cyclin or 
      cyclin-dependent kinase (Cdk) levels when E7-expressing cells were compared to 
      the parental cell line, RKO. Furthermore, Cdk2 kinase activity was inhibited in 
      both RKO cells and E7-expressing cells, while Cdk2 remained active in 
      E6-expressing cells. However, the steady-state levels of pRB and p107 protein 
      were substantially lower in E7-expressing cells than in the parental RKO cells or 
      E6-expressing cells. There was no reduction in pRB mRNA levels, but the half-life 
      of pRB in E7-expressing cells was markedly shorter. Infection of primary human 
      foreskin keratinocytes with recombinant retroviruses expressing HPV-16 E7 
      resulted in a decrease in pRB protein levels, indicating this phenomenon is a 
      consequence of E7 expression, not of immortalization or transformation. These 
      data strongly suggest E7 interferes with the stability of pRB and p107 protein. 
      We propose that the removal of these components of the p53-mediated G1 growth 
      arrest pathway in E7-expressing cells contributes to the ability of E7 to 
      overcome a p53-mediated G1 growth arrest.
FAU - Jones, D L
AU  - Jones DL
AD  - Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, 
      USA.
FAU - Munger, K
AU  - Munger K
LA  - eng
GR  - CA 66980/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  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone)
RN  - 0 (Oligopeptides)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 143313-51-3 (L 709049)
RN  - 1CC1JFE158 (Dactinomycin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (CDK6 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 6)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - *CDC2-CDC28 Kinases
MH  - Cell Cycle
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinase 6
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclin-Dependent Kinases/metabolism
MH  - Cyclins/analysis/metabolism
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - DNA Damage
MH  - Dactinomycin/pharmacology
MH  - *G1 Phase
MH  - Humans
MH  - Oligopeptides/pharmacology
MH  - Oncogene Proteins, Viral/biosynthesis/genetics/metabolism/*physiology
MH  - Papillomaviridae/genetics/*physiology
MH  - Papillomavirus E7 Proteins
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - *Proto-Oncogene Proteins
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - *Repressor Proteins
MH  - Retinoblastoma Protein/metabolism
MH  - Signal Transduction
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*metabolism
PMC - PMC191417
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
PMCR- 1997/04/01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
PHST- 1997/04/01 00:00 [pmc-release]
AID - 10.1128/JVI.71.4.2905-2912.1997 [doi]
PST - ppublish
SO  - J Virol. 1997 Apr;71(4):2905-12. doi: 10.1128/JVI.71.4.2905-2912.1997.