PMID- 10454565
OWN - NLM
STAT- MEDLINE
DCOM- 19990910
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 9
DP  - 1999 Sep
TI  - Ectopic expression of Cdc25A accelerates the G(1)/S transition and leads to
      premature activation of cyclin E- and cyclin A-dependent kinases.
PG  - 6183-94
AB  - Human Cdc25 phosphatases play important roles in cell cycle regulation by
      removing inhibitory phosphates from tyrosine and threonine residues of
      cyclin-dependent kinases. Three human Cdc25 isoforms, A, B, and C, have been
      discovered. Cdc25B and Cdc25C play crucial roles at the G(2)/M transition. In the
      present study, we have investigated the function of human Cdc25A phosphatase.
      Cell lines that express human Cdc25A in an inducible manner have been generated. 
      Ectopic expression of Cdc25A accelerates the G(1)/S-phase transition, indicating 
      that Cdc25A controls an event(s) that is rate limiting for entry into S phase.
      Furthermore, we carried out a detailed analysis of the expression and activation 
      of human Cdc25A. Activation of endogenous Cdc25A occurs during late G(1) phase
      and increases in S and G(2) phases. We further demonstrate that Cdc25A is
      activated at the same time as cyclin E- and cyclin A-dependent kinases. In vitro,
      Cdc25A dephosphorylates and activates the cyclin-Cdk complexes that are active
      during G(1). Overexpression of Cdc25A in the inducible system, however, leads to 
      a premature activation of both cyclin E-Cdk2 and cyclin A-Cdk2 complexes, while
      no effect of cyclin D-dependent kinases is observed. Furthermore, Cdc25A
      overexpression induces a tyrosine dephosphorylation of Cdk2. These results
      suggest that Cdc25A is an important regulator of the G(1)/S-phase transition and 
      that cyclin E- and cyclin A-dependent kinases act as direct targets.
FAU - Blomberg, I
AU  - Blomberg I
AD  - Forschungsschwerpunkt Angewandte Tumorvirologie (F0400), Deutsches
      Krebsforschungszentrum, D-69120 Heidelberg, Germany.
FAU - Hoffmann, I
AU  - Hoffmann I
LA  - eng
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 (CCNG1 protein, human)
RN  - 0 (Ccng1 protein, rat)
RN  - 0 (Cyclin A)
RN  - 0 (Cyclin E)
RN  - 0 (Cyclin G)
RN  - 0 (Cyclin G1)
RN  - 0 (Cyclins)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
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  - Cell Cycle/*physiology
MH  - Cell Line
MH  - Cyclin A/metabolism
MH  - Cyclin E/metabolism
MH  - Cyclin G
MH  - Cyclin G1
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Cyclins/metabolism
MH  - Enzyme Activation
MH  - G1 Phase/physiology
MH  - Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - Protein Tyrosine Phosphatases/genetics/*physiology
MH  - Rats
MH  - S Phase/physiology
MH  - Transfection
MH  - *cdc25 Phosphatases
PMC - PMC84557
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.19.9.6183 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Sep;19(9):6183-94. doi: 10.1128/mcb.19.9.6183.