Office Phone: 318-675-8204
Laboratory Phone: 318-675-6539
Office Fax: 318-675-5180
M.S., St. Petersburg State University, Russia
Ph.D., 1980,St. Petersburg State University, Russia
Assembly of protein synthesis initiation factor complexes; the role of eIF4E phosphorylation in initiation of translation; protein folding; mRNA decay
Dr. Slepenkov's major research interests include the enzymology of protein and nucleic acid unfolding. The role of eukaryotic initiation factor 4E phosphorylation in initiation of protein synthesis.
Translation in eukaryotic cells is a complex and spatially organized process with many steps. Eukaryotic initiation factor 4E (eIF4E) is at the beginning of that process. Regulation of eIF4E activity is very important during the recruitment of capped mRNA and subsequent assembly of the 48 S pre-initiation complex, which then scans for the first AUG. In higher animals, eIF4E is phosphorylated by a specific kinase termed Mnk. How that phosphorylation influences eIF4E function is unknown. We are employing techniques of molecular biology and biophysical chemistry in order to gain insight into the role of eIF4E phosphorylation in regulation of protein synthesis. Also, we are interested in the processes of nucleic acid unwinding and protein folding. Both of these molecular events are necessary for successful completion of protein synthesis, from the assembly of the translation initiation complex to folding of the synthesized nascent chain into a native functional protein. The two processes have elements in common. For example, to start protein synthesis, mRNA during the scanning and elongation phases must be unwound or unfolded by a specific component of the initiation complex, eIF4A, a helicase that couples ATP hydrolysis with mRNA unfolding. In a similar sequence of events, nascent polypeptide chains leaving the ribosome in the absence of Hsp70 and trigger factor are generally misfolded. Protein chaperones of a specific class bind misfolded proteins and, using energy from ATP binding and hydrolysis, are thought to unfold them to provide another opportunity for productive folding. We are studying the mechanisms and kinetics of these reactions.