Zoia R Stoytcheva1, Marla J Berry. 1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Suite 222, Honolulu, HI 96813, USA.
Abstract
BACKGROUND: Selenoproteins contain the twenty-first amino acid, selenocysteine, and are involved in cellular defenses against oxidative damage, important metabolic and developmental pathways, and responses to environmental challenges. Elucidating the mechanisms regulating selenoprotein expression at the transcriptional level is a key to understanding how these mechanisms are called into play to respond to the changing environment. METHODS: This review summarizes published studies on transcriptional regulation of selenoprotein genes, focused primarily on genes whose encoded protein functions are at least partially understood. This is followed by in silico analysis of predicted regulatory elements in selenoprotein genes, including those in the aforementioned category as well as the genes whose functions are not known. RESULTS: Our findings reveal regulatory pathways common to many selenoprotein genes, including several involved in stress-responses. In addition, tissue-specific regulatory factors are implicated in regulating many selenoprotein genes. CONCLUSIONS: These studies provide new insights into how selenoprotein genes respond to environmental and other challenges, and the roles these proteins play in allowing cells to adapt to these changes. GENERAL SIGNIFICANCE: Elucidating the regulatory mechanisms affecting selenoprotein expression is essential for understanding their roles in human diseases, and for developing diagnostic and potential therapeutic approaches to address dysregulation of members of this gene family.
BACKGROUND:Selenoproteins contain the twenty-first amino acid, selenocysteine, and are involved in cellular defenses against oxidative damage, important metabolic and developmental pathways, and responses to environmental challenges. Elucidating the mechanisms regulating selenoprotein expression at the transcriptional level is a key to understanding how these mechanisms are called into play to respond to the changing environment. METHODS: This review summarizes published studies on transcriptional regulation of selenoprotein genes, focused primarily on genes whose encoded protein functions are at least partially understood. This is followed by in silico analysis of predicted regulatory elements in selenoprotein genes, including those in the aforementioned category as well as the genes whose functions are not known. RESULTS: Our findings reveal regulatory pathways common to many selenoprotein genes, including several involved in stress-responses. In addition, tissue-specific regulatory factors are implicated in regulating many selenoprotein genes. CONCLUSIONS: These studies provide new insights into how selenoprotein genes respond to environmental and other challenges, and the roles these proteins play in allowing cells to adapt to these changes. GENERAL SIGNIFICANCE: Elucidating the regulatory mechanisms affecting selenoprotein expression is essential for understanding their roles in human diseases, and for developing diagnostic and potential therapeutic approaches to address dysregulation of members of this gene family.
Authors: Monica Dentice; Cristina Luongo; Stephen Huang; Raffaele Ambrosio; Antonia Elefante; Delphine Mirebeau-Prunier; Ann Marie Zavacki; Gianfranco Fenzi; Marina Grachtchouk; Mark Hutchin; Andrzej A Dlugosz; Antonio C Bianco; Caterina Missero; P Reed Larsen; Domenico Salvatore Journal: Proc Natl Acad Sci U S A Date: 2007-08-24 Impact factor: 11.205
Authors: FuKun W Hoffmann; Ann S Hashimoto; Byung Cheon Lee; Aaron H Rose; Ralph V Shohet; Peter R Hoffmann Journal: Arch Biochem Biophys Date: 2011-05-20 Impact factor: 4.013