PMID- 10444066
OWN - NLM
STAT- MEDLINE
DCOM- 19990901
LR  - 20191023
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 146
IP  - 3
DP  - 1999 Aug 9
TI  - Cdc25B and Cdc25C differ markedly in their properties as initiators of mitosis.
PG  - 573-84
AB  - We have used time-lapse fluorescence microscopy to study the properties of the
      Cdc25B and Cdc25C phosphatases that have both been implicated as initiators of
      mitosis in human cells. To differentiate between the functions of the two
      proteins, we have microinjected expression constructs encoding Cdc25B or Cdc25C
      or their GFP-chimeras into synchronized tissue culture cells. This assay allows
      us to express the proteins at defined points in the cell cycle. We have followed 
      the microinjected cells by time-lapse microscopy, in the presence or absence of
      DNA synthesis inhibitors, and assayed whether they enter mitosis prematurely or
      at the correct time. We find that overexpressing Cdc25B alone rapidly causes S
      phase and G2 phase cells to enter mitosis, whether or not DNA replication is
      complete, whereas overexpressing Cdc25C does not cause premature mitosis.
      Overexpressing Cdc25C together with cyclin B1 does shorten the G2 phase and can
      override the unreplicated DNA checkpoint, but much less efficiently than
      overexpressing Cdc25B. These results suggest that Cdc25B and Cdc25C do not
      respond identically to the same cell cycle checkpoints. This difference may be
      related to the differential localization of the proteins; Cdc25C is nuclear
      throughout interphase, whereas Cdc25B is nuclear in the G1 phase and cytoplasmic 
      in the S and G2 phases. We have found that the change in subcellular localization
      of Cdc25B is due to nuclear export and that this is dependent on cyclin B1. Our
      data suggest that although both Cdc25B and Cdc25C can promote mitosis, they are
      likely to have distinct roles in the controlling the initiation of mitosis.
FAU - Karlsson, C
AU  - Karlsson C
AD  - Wellcome/CRC Institute, Cambridge CB2 1QR United Kingdom.
FAU - Katich, S
AU  - Katich S
FAU - Hagting, A
AU  - Hagting A
FAU - Hoffmann, I
AU  - Hoffmann I
FAU - Pines, J
AU  - Pines J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (CCNB1 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin B)
RN  - 0 (Cyclin B1)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (WEE1 protein, human)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.48 (CDC25B protein, human)
RN  - EC 3.1.3.48 (CDC25C protein, human)
RN  - EC 3.1.3.48 (cdc25 Phosphatases)
SB  - IM
MH  - Biological Transport
MH  - CDC2 Protein Kinase/antagonists & inhibitors/genetics/metabolism
MH  - Cell Cycle Proteins/genetics/*metabolism
MH  - Cell Nucleus/enzymology/genetics
MH  - Chromosomes/genetics/metabolism
MH  - Cyclin B/genetics/metabolism
MH  - Cyclin B1
MH  - Cytoplasm/enzymology
MH  - DNA/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - Interphase
MH  - Microinjections
MH  - Microscopy, Fluorescence
MH  - *Mitosis
MH  - Mutation
MH  - *Nuclear Proteins
MH  - Phosphoprotein Phosphatases/genetics/*metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Time Factors
MH  - *cdc25 Phosphatases
PMC - PMC2150562
EDAT- 1999/08/12 00:00
MHDA- 1999/08/12 00:01
CRDT- 1999/08/12 00:00
PHST- 1999/08/12 00:00 [pubmed]
PHST- 1999/08/12 00:01 [medline]
PHST- 1999/08/12 00:00 [entrez]
AID - 10.1083/jcb.146.3.573 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Aug 9;146(3):573-84. doi: 10.1083/jcb.146.3.573.