Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1).
The regulation of divalent zinc has been observed in a wide range of organisms. Since this metal is an essential nutrient, but also toxic in excess, zinc homeostasis is crucial for normal cellular functioning. The metal-responsive-element-binding transcription factor-1 (MTF-1) is a key regulator of zinc in higher eukaryotes ranging from insects to mammals. MTF-1 controls the expression of metallothioneins (MTs) and a number of other genes directly involved in the intracellular sequestration and transport of zinc. Although the diverse functions of MTF-1 extend well beyond zinc homeostasis to include stress-responses to heavy metal toxicity, oxidative stress, and selected chemical agents, in this review we focus on the recent advances in understanding the mechanisms whereby MTF-1 regulates MT gene expression to protect the cell from fluctuations in environmental zinc. Particular emphasis is devoted to recent studies involving the Cys2His2 zinc finger DNA-binding domain of MTF-1, which is an important contributor to the zinc-sensing and metal-dependent transcriptional activation functions of this protein.
Laity
John H
JH
Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110-2499, USA. laityj@umkc.edu
Andrews
Glen K
GK
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008668:Metallothionein / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*; D016335:Zinc Fingers; D000097809:Transcription Factor MTF-1
D004268:DNA-Binding Proteins; D008668:Metallothionein; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1