Sergey Slepenkov, Ph.D.

Assistant Professor-Research


Contact Information:

Email: sslepe@lsuhsc.edu
Office Phone: 318-675-8204
Laboratory Phone: 318-675-6539
Office Fax: 318-675-5180

Education/Training:

M.S., St. Petersburg State University, Russia
Ph.D., 1980,St. Petersburg State University, Russia

Major Research Interests:

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.

Representative Publications

  1. Synthetic mRNAs with superior translation and stability properties.
  2. mRNAs containing the histone 3' stem-loop are degraded primarily by decapping mediated by oligouridylation of the 3' end.
  3. Helicobacter pylori AlpA and AlpB bind host laminin and influence gastric inflammation in gerbils.
  4. Translation, stability, and resistance to decapping of mRNAs containing caps substituted in the triphosphate chain with BH3, Se, and NH.
  5. Kinetic mechanism for assembly of the m7GpppG.eIF4E.eIF4G complex.

All Publications: PubMed or Full List Here