title: PTEN interacts with metal-responsive transcription factor 1 and stimulates its transcriptional activity.
abstract: MTF-1 (metal-responsive transcription factor 1) is an essential mammalian protein for embryonic development and modulates the expression of genes involving in zinc homoeostasis and responding to oxidative stress. We report in the present paper that PTEN (phosphatase and tensin homologue deleted on chromosome 10) associates with MTF-1 in the cells. These two proteins interact via the acidic domain of MTF-1 and the phosphatase/C2 domain of PTEN. Depletion of PTEN reduced MT (metallothionein) gene expression and increased cellular sensitivity to cadmium toxicity. PTEN did not alter the nuclear translocation, protein stability or DNA-binding activity of MTF-1. Zinc increased MTF-1-PTEN interaction in a dose-dependent manner. The interaction elevated within 2 h of zinc addition and declined afterwards in the cells. The enhanced binding activity occurred mainly in the cytoplasm and reduced after translocating the MTF-1 into the nucleus. Blocking signalling through the PI3K (phosphoinositide 3-kinase) pathway did not alter the zinc-induced MT expression. Analysis of enzymatically inactive PTEN mutants demonstrated that protein but not lipid phosphatase activity of PTEN was involved in the regulation of MTF-1 activity. The same regulatory role of PTEN was also noted in the regulation of ZnT1 (zinc transporter 1), another target gene of MTF-1.
authors: Department of Life Science and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Meng-Chieh
authors: MC
authors: Lin
authors: Ya-Chuan
authors: YC
authors: Liu
authors: Ming F
authors: MF
authors: Tam
authors: Yu-Ju
authors: YJ
authors: Lu
authors: Ya-Ting
authors: YT
authors: Hsieh
authors: Lih-Yuan
authors: LY
authors: Lin
mesh_terms: D000818:Animals; D016466:CHO Cells; D002104:Cadmium; D027682:Cation Transport Proteins; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D015032:Zinc / Q000378:metabolism; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D008668:Metallothionein; D051059:PTEN Phosphohydrolase; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C485803:Slc30a1 protein, mouse; C487757:Pten protein, mouse