PMID- 10069470
OWN - NLM
STAT- MEDLINE
DCOM- 19990311
LR  - 20190513
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 20
IP  - 2
DP  - 1999 Feb
TI  - Expression cloning for arsenite-resistance resulted in isolation of
      tumor-suppressor fau cDNA: possible involvement of the ubiquitin system in
      arsenic carcinogenesis.
PG  - 311-6
AB  - Arsenic is a human carcinogen whose mechanism of action is unknown. Previously,
      this laboratory demonstrated that arsenite acts as a comutagen by interfering
      with DNA repair, although a specific DNA repair enzyme sensitive to arsenite has 
      not been identified. A number of stable arsenite-sensitive and arsenite-resistant
      sublines of Chinese hamster V79 cells have now been isolated. In order to gain
      understanding of possible targets for arsenite's action, one arsenite-resistant
      subline, As/R28A, was chosen as a donor for a cDNA expression library. The
      library from arsenite-induced As/R28A cells was transfected into
      arsenite-sensitive As/S5 cells, and transfectants were selected for
      arsenite-resistance. Two cDNAs, asr1 and asr2, which confer arsenite resistance
      to arsenite-hypersensitive As/S5 cells as well as to wild-type cells, were
      isolated. asr1 shows almost complete homology with the rat fau gene, a tumor
      suppressor gene which contains a ubiquitin-like region fused to S30 ribosomal
      protein. Arsenite was previously shown to inhibit ubiquitin-dependent
      proteolysis. These results suggest that the tumor suppressor fau gene product or 
      some other aspect of the ubiquitin system may be a target for arsenic toxicity
      and that disruption of the ubiquitin system may contribute to the genotoxicity
      and carcinogenicity of arsenite.
FAU - Rossman, T G
AU  - Rossman TG
AD  - Nelson Institute of Environmental Medicine and Kaplan Comprehensive Cancer
      Center, New York University Medical Center, NY 10016, USA.
      rossman@charlotte.mid.nyu.edu
FAU - Wang, Z
AU  - Wang Z
LA  - eng
SI  - GENBANK/U41499
SI  - GENBANK/U41500
GR  - CA57352/CA/NCI NIH HHS/United States
GR  - ES 00260/ES/NIEHS NIH HHS/United States
GR  - ES09252/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (ASNA1 protein, human)
RN  - 0 (Arsenites)
RN  - 0 (DNA, Complementary)
RN  - 0 (Ribosomal Proteins)
RN  - 0 (Teratogens)
RN  - EC 3.6.3.16 (Arsenite Transporting ATPases)
RN  - N5509X556J (arsenite)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arsenite Transporting ATPases
MH  - Arsenites/*toxicity
MH  - Base Sequence
MH  - Cells, Cultured/drug effects
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA, Complementary/genetics/*isolation & purification
MH  - Drug Resistance/genetics
MH  - Genes, Tumor Suppressor
MH  - Molecular Sequence Data
MH  - Rats
MH  - Ribosomal Proteins/genetics/*isolation & purification
MH  - Teratogens/*toxicity
MH  - Transfection
EDAT- 1999/03/09 00:00
MHDA- 1999/03/09 00:01
CRDT- 1999/03/09 00:00
PHST- 1999/03/09 00:00 [pubmed]
PHST- 1999/03/09 00:01 [medline]
PHST- 1999/03/09 00:00 [entrez]
AID - 10.1093/carcin/20.2.311 [doi]
PST - ppublish
SO  - Carcinogenesis. 1999 Feb;20(2):311-6. doi: 10.1093/carcin/20.2.311.