PMID- 10613832
OWN - NLM
STAT- MEDLINE
DCOM- 20000209
LR  - 20061115
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 6
IP  - 1
DP  - 2000 Jan
TI  - Reduced stability of retinoblastoma protein by gankyrin, an oncogenic
      ankyrin-repeat protein overexpressed in hepatomas.
PG  - 96-9
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers in Asia and
      Africa, where hepatitis virus infection and exposure to specific liver
      carcinogens are prevalent. Although inactivation of some tumor suppressor genes
      such as p53 and p16INK4Ahas been identified, no known oncogene is commonly
      activated in hepatocellular carcinomas. Here we have isolated genes overexpressed
      in hepatocellular carcinomas by cDNA subtractive hybridization, and identified an
      oncoprotein consisting of six ankyrin repeats (gankyrin). The expression of
      gankyrin was increased in all 34 hepatocellular carcinomas studied. Gankyrin
      induced anchorage-independent growth and tumorigenicity in NIH/3T3 cells.
      Gankyrin bound to the product of the retinoblastoma gene (RB1), increasing its
      phosphorylation and releasing the activity of the transcription factor E2F-1.
      Gankyrin accelerated the degradation of RB1 in vitro and in vivo, and was
      identical to or interacted with a subunit of the 26S proteasome. These results
      demonstrate the importance of ubiquitin-proteasome pathway in the regulation of
      cell growth and oncogenic transformation, and indicate that gankyrin
      overexpression contributes to hepatocarcinogenesis by destabilizing RB1.
FAU - Higashitsuji, H
AU  - Higashitsuji H
AD  - Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, 
      54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Itoh, K
AU  - Itoh K
FAU - Nagao, T
AU  - Nagao T
FAU - Dawson, S
AU  - Dawson S
FAU - Nonoguchi, K
AU  - Nonoguchi K
FAU - Kido, T
AU  - Kido T
FAU - Mayer, R J
AU  - Mayer RJ
FAU - Arii, S
AU  - Arii S
FAU - Fujita, J
AU  - Fujita J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Oncogene Proteins)
RN  - 0 (PSMD10 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.4.99.- (ATP dependent 26S protease)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Carcinoma, Hepatocellular/genetics/*metabolism/pathology
MH  - Cell Division
MH  - Cloning, Molecular
MH  - Genes, Reporter
MH  - Genes, Retinoblastoma
MH  - HeLa Cells
MH  - Humans
MH  - Kinetics
MH  - Liver/*metabolism/pathology
MH  - Liver Neoplasms/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Oncogene Proteins/genetics/*metabolism
MH  - Peptide Hydrolases/metabolism
MH  - *Proteasome Endopeptidase Complex
MH  - Proto-Oncogene Proteins
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Retinoblastoma Protein/*metabolism
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 1999/12/29 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/29 09:00
PHST- 1999/12/29 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/29 09:00 [entrez]
AID - 10.1038/71600 [doi]
PST - ppublish
SO  - Nat Med. 2000 Jan;6(1):96-9. doi: 10.1038/71600.