TY - JOUR
T1 - Trivalent arsenic inhibits the functions of chaperonin complex
AU - Pan, Xuewen
AU - Reissman, Stefanie
AU - Douglas, Nick R.
AU - Huang, Zhiwei
AU - Yuan, Daniel S.
AU - Wang, Xiaoling
AU - McCaffery, J. Michael
AU - Frydman, Judith
AU - Boeke, Jef D.
PY - 2010/10
Y1 - 2010/10
N2 - The exact molecular mechanisms by which the environmental pollutant arsenic works in biological systems are not completely understood. Using an unbiased chemogenomics approach in Saccharomyces cerevisiae, we found that mutants of the chaperonin complex TRiC and the functionally related prefoldin complex are all hypersensitive to arsenic compared to a wild-type strain. In contrast, mutants with impaired ribosome functions were highly arsenic resistant. These observations led us to hypothesize that arsenic might inhibit TRiC function, required for folding of actin, tubulin, and other proteins postsynthesis. Consistent with this hypothesis, we found that arsenic treatment distorted morphology of both actin and microtubule filaments. Moreover, arsenic impaired substrate folding by both bovine and archaeal TRiC complexes in vitro. These results together indicate that TRiC is a conserved target of arsenic inhibition in various biological systems.
AB - The exact molecular mechanisms by which the environmental pollutant arsenic works in biological systems are not completely understood. Using an unbiased chemogenomics approach in Saccharomyces cerevisiae, we found that mutants of the chaperonin complex TRiC and the functionally related prefoldin complex are all hypersensitive to arsenic compared to a wild-type strain. In contrast, mutants with impaired ribosome functions were highly arsenic resistant. These observations led us to hypothesize that arsenic might inhibit TRiC function, required for folding of actin, tubulin, and other proteins postsynthesis. Consistent with this hypothesis, we found that arsenic treatment distorted morphology of both actin and microtubule filaments. Moreover, arsenic impaired substrate folding by both bovine and archaeal TRiC complexes in vitro. These results together indicate that TRiC is a conserved target of arsenic inhibition in various biological systems.
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U2 - 10.1534/genetics.110.117655
DO - 10.1534/genetics.110.117655
M3 - Article
C2 - 20660648
AN - SCOPUS:78951481256
SN - 0016-6731
VL - 186
SP - 725
EP - 734
JO - Genetics
JF - Genetics
IS - 2
ER -