PMID- 10454584
OWN - NLM
STAT- MEDLINE
DCOM- 19990910
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 9
DP  - 1999 Sep
TI  - CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S
      phase.
PG  - 6379-95
AB  - Functional inactivation of the pRB pathway is a very frequent event in human
      cancer, resulting in deregulated activity of the E2F transcription factors. To
      understand the functional role of the E2Fs in cell proliferation, we have
      developed cell lines expressing E2F-1, E2F-2, and E2F-3 fused to the estrogen
      receptor ligand binding domain (ER). In this study, we demonstrated that
      activation of all three E2Fs could relieve the mitogen requirement for entry into
      S phase in Rat1 fibroblasts and that E2F activity leads to a shortening of the
      G(0)-G(1) phase of the cell cycle by 6 to 7 h. In contrast to the current
      assumption that E2F-1 is the only E2F capable of inducing apoptosis, we showed
      that deregulated E2F-2 and E2F-3 activities also result in apoptosis. Using the
      ERE2F-expressing cell lines, we demonstrated that several genes containing E2F
      DNA binding sites are efficiently induced by the E2Fs in the absence of protein
      synthesis. Furthermore, CDC25A is defined as a novel E2F target whose expression 
      can be directly regulated by E2F-1. Data showing that CDC25A is an essential
      target for E2F-1, since its activity is required for efficient induction of S
      phase by E2F-1, are provided. Finally, our results show that expression of two
      E2F target genes, namely CDC25A and cyclin E, is sufficient to induce entry into 
      S phase in quiescent fibroblasts. Taken together, our results provide an
      important step in defining how E2F activity leads to deregulated proliferation.
FAU - Vigo, E
AU  - Vigo E
AD  - Department of Experimental Oncology, European Institute of Oncology, 20141 Milan,
      Italy.
FAU - Muller, H
AU  - Muller H
FAU - Prosperini, E
AU  - Prosperini E
FAU - Hateboer, G
AU  - Hateboer G
FAU - Cartwright, P
AU  - Cartwright P
FAU - Moroni, M C
AU  - Moroni MC
FAU - Helin, K
AU  - Helin K
LA  - eng
SI  - GENBANK/AJ242714
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Cyclin E)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (E2F1 Transcription Factor)
RN  - 0 (E2F1 protein, human)
RN  - 0 (E2F2 Transcription Factor)
RN  - 0 (E2F2 protein, human)
RN  - 0 (E2F3 Transcription Factor)
RN  - 0 (E2f1 protein, rat)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
RN  - EC 3.1.3.48 (CDC25A protein, human)
RN  - EC 3.1.3.48 (Cdc25a protein, rat)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (cdc25 Phosphatases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Base Sequence
MH  - Binding Sites
MH  - *Carrier Proteins
MH  - *Cell Cycle Proteins
MH  - Cell Division
MH  - Cell Line
MH  - Cyclin E/metabolism
MH  - DNA Primers/genetics
MH  - DNA, Complementary/genetics
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - E2F1 Transcription Factor
MH  - E2F2 Transcription Factor
MH  - E2F3 Transcription Factor
MH  - Gene Targeting
MH  - Humans
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Protein Tyrosine Phosphatases/genetics/*metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Retinoblastoma Protein/metabolism
MH  - Retinoblastoma-Binding Protein 1
MH  - S Phase/*physiology
MH  - Transcription Factor DP1
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - *cdc25 Phosphatases
PMC - PMC84608
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1128/mcb.19.9.6379 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Sep;19(9):6379-95. doi: 10.1128/mcb.19.9.6379.