Molecular & Cellular Biochemistry Section
Building 30 Room 3A300
30 Convent Dr MSC 4340
Bethesda, MD 20892-4340
Dr. Myung Hee Park studies the role of a polyamine-modified cellular protein—eukaryotic translation factor 5A (eIF5A) -- in the regulation of eukaryotic protein synthesis, cell proliferation, and tumorigenesis. 5A(eIF5A) contains an amino acid known as hypusine. Hypusine modification is vital for protein synthesis and cell proliferation and offers a novel target for intervention in aberrant cell growth, such as cancer. Dr. Park’s group established the enzymatic steps of hypusine synthesis involving the polyamine spermidine, and cloned and characterized the mechanisms and structural properties of the two enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). The group is developing inhibitors of DHS and DOHH through rational design and high throughput screening for use in treatments for diseases in which eIF5A has been implicated. Dr. Park also investigates the function and the mechanism of action of polycationic polyamines in the regulation of cellular proliferation, differentiation, and transformation.
Dr. Park received her BS from Seoul National University, Korea, and her PhD in chemistry from Brown University. Dr. Park completed her postdoctoral work in cell biology at the Massachusetts Institute of Technology. In 1979, she joined the Laboratory of Biochemistry at NIDCR as a visiting fellow and discovered a novel posttranslational modification pathway that converts a specific lysine of the eukaryotic translation factor, eIF5A, to hypusine by the polyamine spermidine. Dr. Park was appointed chief of the Molecular and Cellular Biochemistry in NIDCR in 1998. Dr. Park is recognized for her pioneering research on the hypusine modification of eIF5A and on the functions of polyamines and eIF5A as key regulators in mammalian cells
- Mandal S, Mandal A, Park MH. Depletion of the polyamines spermidine and spermine by overexpression of spermidine/spermine N¹-acetyltransferase 1 (SAT1) leads to mitochondria-mediated apoptosis in mammalian cells. Biochem. J. 2015, 468(3): 435-447.
- Mandal S, Mandal A, Johansson HE, Orjalo AV, Park MH. Depletion of cellular polyamines, spermidine and spermine, causes a total arrest in translation and growth in mammalian cells. Proc. Natl. Acad. Sci. USA. 2013, 110, 2169-2174.
- Park MH, Cooper HL, Folk JE. Identification of hypusine, an unusual amino acid, in a protein from human lymphocytes and of spermidine as its biosynthetic precursor. Proc. Natl. Acad. Sci. USA 1981 May; 78:2869-2873.
- Cooper HL, Park MH, Folk JE. Posttranslational formation of hypusine in a single major protein occurs generally in growing cells and is associated with activation of lymphocyte growth. Cell. 1982 Jul, 29:791-797. PMID: 6817926
- Park MH. The essential role of hypusine in eukaryotic translation initiation factor 4D (eIF-4D): purification of eIF-4D and its precursors and comparison of their activities. J Biol Chem. 1989 Nov 5; 264(31):18531-18535.
- Park MH, Wolff EC, Lee YB, Folk JE. Antiproliferative effects of inhibitors of deoxyhypusine synthase: inhibition of growth of Chinese hamster ovary cells by guanyl diamines. J Biol Chem. 1994 Nov 11;269(45):27827-27832.
- Joe YA, Wolff EC, Park MH. Cloning and expression of human deoxyhypusine synthase cDNA: structure-function studies with the recombinant enzyme and mutant proteins. J Biol Chem. 1995 Sep22;270:22386-22393.
- Joe YA, Wolff EC, Lee YB, Park MH. Enzyme-substrate intermediate at a specific lysine residue is required for deoxyhypusine synthesis: the role of Lys329 in human deoxyhypusine synthase. J Biol Chem. 1997 Dec 19;272(51): 32679-326785.
- Park, JH, Aravind L, Wolff EC, Kaevel J, Kim YS, Park MH. Molecular cloning, expression and structural prediction of deoxyhypusine hydroxylase: a novel HEAT-repeat-containing metalloenzyme. Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):51-56.
- Kim YS, Kang KR, Wolff EC, Bell JK, McPhie P, Park MH. Deoxyhypusine hydroxylase is a Fe(II)-dependent HEAT-repeat enzyme: Identification of amino acid residues critical for Fe(II) binding and catalysis. J Biol Chem 2006 May 12;281(19):13217-13225.