PMID- 12669309
OWN - NLM
STAT- MEDLINE
DCOM- 20030423
LR  - 20091119
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 36
IP  - 4
DP  - 2003 Apr
TI  - Inhibition of proteasome-dependent degradation of Wee1 in G2-arrested Hep3B cells 
      by TGF beta 1.
PG  - 171-82
AB  - Transforming growth factor beta1 (TGF beta 1)-induced G2 arrest was observed when 
      a proliferation inhibitory function of the retinoblastoma protein (Rb) was 
      compromised, but the mechanism underlying the G2 arrest was poorly characterized 
      compared with that of G1 arrest. In the present study, we characterized G2 arrest 
      induced by TGF beta1 (1 ng/mL) in the Rb-negative hepatoma cell line (Hep3B) and 
      compared with G1 arrest in the Rb-positive hepatoma cell line (Huh7). Activities 
      of cyclin-dependent kinases (CDK) 2 and cell division cycle (CDC) 2 were markedly 
      decreased at 24 h, the time when cell-cycle arrest became apparent in both cell 
      lines. However, considerable amounts of inactive CDC2-cyclinB1 complexes were 
      present in the nucleus of G2-arrested Hep3B but were not present in G1-arrested 
      Huh7. The inhibitory phosphorylation of CDC2 on Tyr-15 was significantly elevated 
      at 12-24 h, and its levels gradually declined during G2 arrest in Hep3B. In 
      particular, augmentation of CDK inhibitors p21cip1 and p27kip1 and Wee1 kinase 
      and diminution of CDC25C phosphatase coincided with induced Tyr-15 
      phosphorylation and inhibition of CDC2. Wee1 in Hep3B was unstable and was 
      degraded in a proteasome-dependent manner, but it became substantially stabilized 
      within 6 h of TGF beta 1 treatment. Moreover, a Wee1 inhibitor, PD0166285, 
      abrogated the TGF beta 1-induced G2 arrest in Hep3B. These findings suggest that 
      TGF beta 1 induced G2 arrest in Hep3B at least in part through stabilization of 
      Wee1 and subsequent increase in Tyr-15 phosphorylation and inhibition of CDC2.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Hashimoto, Osamu
AU  - Hashimoto O
AD  - Liver Cancer Research Division, Research Center for Innovative Cancer Therapy, 
      Kurume University School of Medicine, Kurume, Japan.
FAU - Ueno, Takato
AU  - Ueno T
FAU - Kimura, Rina
AU  - Kimura R
FAU - Ohtsubo, Motoaki
AU  - Ohtsubo M
FAU - Nakamura, Toru
AU  - Nakamura T
FAU - Koga, Hironori
AU  - Koga H
FAU - Torimura, Takuji
AU  - Torimura T
FAU - Uchida, Sanae
AU  - Uchida S
FAU - Yamashita, Katsumi
AU  - Yamashita K
FAU - Sata, Michio
AU  - Sata M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (WEE1 protein, human)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Base Sequence
MH  - Carcinoma, Hepatocellular
MH  - Cell Cycle/*drug effects
MH  - *Cell Cycle Proteins
MH  - Cell Division/drug effects
MH  - Cysteine Endopeptidases
MH  - DNA Primers
MH  - G2 Phase/drug effects
MH  - Humans
MH  - Kinetics
MH  - Liver Neoplasms
MH  - Multienzyme Complexes/*antagonists & inhibitors
MH  - Nuclear Proteins/metabolism
MH  - Phosphorylation
MH  - Proteasome Endopeptidase Complex
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Transforming Growth Factor beta1
MH  - Tumor Cells, Cultured
EDAT- 2003/04/02 05:00
MHDA- 2003/04/24 05:00
CRDT- 2003/04/02 05:00
PHST- 2003/04/02 05:00 [pubmed]
PHST- 2003/04/24 05:00 [medline]
PHST- 2003/04/02 05:00 [entrez]
AID - 10.1002/mc.10111 [doi]
PST - ppublish
SO  - Mol Carcinog. 2003 Apr;36(4):171-82. doi: 10.1002/mc.10111.