PMID- 10504341
OWN - NLM
STAT- MEDLINE
DCOM- 19991217
LR  - 20161124
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 112 ( Pt 19)
DP  - 1999 Oct
TI  - The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2
      complexes and is required for inhibition of G(2)/M progression.
PG  - 3361-71
AB  - Activation of Cdc2, is the universal event controlling the onset of mitosis. In
      higher eukaryotes, Cdc2 activity is in part regulated by inhibitory
      phosphorylation of Thr14 and Tyr15, catalyzed by Wee1 and Myt1, which prevents
      catastrophic premature entry into mitosis. In this study we defined the function 
      of Myt1 by overexpression studies in both S. pombe and a human osteosarcoma cell 
      line. Similar to Wee1, overexpression of human Myt1 prevented entry into mitosis 
      in both cell types; however, Myt1 catalytic activity was not essential for the
      cell cycle delay observed with human cells. Myt1 expression was restricted to
      proliferating cells. Furthermore, we detected no major decline in Myt1 protein
      abundance prior to the entry into mitosis, which coincides with the loss of Myt1 
      activity. We localized mitotic phosphoepitopes, recognized by the monoclonal
      antibody MPM-2, to the C-terminal domain of Myt1. The mitotic peptidyl-prolyl
      isomerase, Pin1, was able to associate with this domain in a
      phosphorylation-dependent manner. Truncation of the C-terminal domain of Myt1
      prevented its ability to induce G(2)/M phase arrest in overexpression studies in 
      human cells and dramatically reduced its ability to phosphorylate Cdc2 in vitro. 
      We demonstrate that the C-terminal domain of Myt1 was required for recruitment of
      Cdc2, and we infer that this domain lies in the cytoplasm because it can interact
      with and is phosphorylated by Cdc2. In conclusion, we propose that Myt1 can
      negatively regulate Cdc2/cyclin B1 and inhibit G(2)/M progression by two means,
      both of which require the C-terminal domain; first, Myt1 can bind and sequester
      Cdc2/cyclin B1 in the cytoplasm preventing entry into the nucleus, and, second,
      it can phosphorylate associated Cdc2/cyclin B1 at Thr14 and Tyr15 thus inhibiting
      its catalytic activity.
FAU - Wells, N J
AU  - Wells NJ
AD  - Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla,
      California 92037, USA.
FAU - Watanabe, N
AU  - Watanabe N
FAU - Tokusumi, T
AU  - Tokusumi T
FAU - Jiang, W
AU  - Jiang W
FAU - Verdecia, M A
AU  - Verdecia MA
FAU - Hunter, T
AU  - Hunter T
LA  - eng
GR  - CA14195/CA/NCI NIH HHS/United States
GR  - CA39780/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  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Biomarkers)
RN  - 0 (Epitopes)
RN  - 0 (Membrane Proteins)
RN  - 0 (NIMA-Interacting Peptidylprolyl Isomerase)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (PKMYT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 5.2.1.8 (PIN1 protein, human)
RN  - EC 5.2.1.8 (Peptidylprolyl Isomerase)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Biomarkers
MH  - CDC2 Protein Kinase/*chemistry/*metabolism
MH  - Catalytic Domain/genetics
MH  - Enzyme Activation/physiology
MH  - Epitopes/immunology
MH  - G2 Phase/*physiology
MH  - Gene Expression Regulation, Fungal
MH  - Humans
MH  - Membrane Proteins
MH  - Mitosis/physiology
MH  - Mutagenesis, Site-Directed/physiology
MH  - NIMA-Interacting Peptidylprolyl Isomerase
MH  - Peptidylprolyl Isomerase/metabolism
MH  - Phosphoproteins/immunology
MH  - Phosphorylation
MH  - Protein Structure, Tertiary
MH  - Protein-Serine-Threonine Kinases/*chemistry/genetics/*metabolism
MH  - Protein-Tyrosine Kinases/*chemistry/genetics/*metabolism
MH  - Schizosaccharomyces/cytology/enzymology
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
PST - ppublish
SO  - J Cell Sci. 1999 Oct;112 ( Pt 19):3361-71.