Section: Research

Qichang Shen, Ph.D.

Faculty Appointment(s) In:
   Pediatrics

Translational regulation of human cellular glutathione peroxidase and its application to regulation of heterologous gene expression

Our research goal is to understand the gene expression and regulation, at the translational level, of human cytosol glutathione peroxidase (GPx). GPx is an important cellular defence component against the toxic peroxide radicals generated in the oxygen metabolism.

It contains at its active site an unusual amino acid selenocysteine coded by the UGA codon, which is otherwise one of the three translation termination codons. We have demonstrated that an sequence element called selenocysteine insertion sequence, located in the 3'- untranslated region of GPx mRNA and postulated to possess a potential stem-loop secondary structure, is not only necessary but also sufficient for signaling the incorporation of selenocysteine into GPx polypeptide chain at the UGA codon. We have also demonstrated that cytosol proteins in cultured COS-1 and many others cell lines, such as Hela cells specifically recognize this sequence element. We are now in the process of cloning these selenocysteine insertion sequence binding proteins. Moreover, we are also interested in the applying this unique selenocysteine insertion system to regulation of heterologous gene expression at the translational level, and to site-specific protein labeling with the rare amino acid selenocysteine. In cooperation with Dr. Jack Leonard in Nuclear Medicine Department of UMMS, we have demonstrated that, in the presence of seleium source in the cell growth medium, the GPx selenocysteine insertion sequence element is able to direct in vivo synthesis of selenocysteine-substituted polypeptide chains of several non-selenoproteins when a chosen cysteine codon is replaced by UGA in the open reading frame of each corresponding mRNA of these proteins. in tested target proteins including rat growth hormone receptor and human thyroid hormone receptor B₁, the selenocysteine substitution has little or no effect on the function of these proteins.

Office: LRB 340E
Phone: 508-856-6791
E-mail: Qichang.Shen@umassmed.edu

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