Muge Martinez, Ph.D.
Postdoctoral Fellow
Funding: NRSA postdoctoral fellowship, NIH (NIAMS); American Heart Association Development Award
e-mail: muge@bcm.tmc.edu
Phone: 713-798-5021
Joined the lab: January, 2004
Research Interests
Myotonic dystrophy 1 (DM1) is the most common adult onset muscular dystrophy affecting multiple systems including skeletal muscle, heart and central nervous system. The RNA transcribed from an expansion of a CTG repeat has a toxic gain of function, which forms ribonuclear inclusions in the nucleus and alters the functions of RNA binding proteins. CUGBP1 is one of the RNA binding proteins implicated in DM1 pathogenesis. CUGBP1 levels are increased in DM1 heart, skeletal muscle tissues and myoblasts. I have recently demonstrated that the mechanism for increased CUGBP1 levels in DM1 is due to PKC mediated phosphorylation, which increases the half-life of the protein. In collaboration with Dr. Wang in the lab, we showed that PKC a / b II activation, CUGBP1 phosphorylation and increase were early events in DM1 heart pathogenesis in an inducible DM1 mouse model expressing 960CUG repeats in the heart. Our findings indicate that PKC-mediated phosphorylation stabilizes the protein. However, the mechanism for this stabilization induced by phosphorylation is unknown. Right now, I am working on understanding the possible mechanisms involved in CUGBP1 stability.
Publications
Wang, G.S., Kuyumcu-Martinez, N.M., Mathur, N., Wehrens, X.H., and Cooper, T.A. (2009) Protein kinase C inhibition ameliorates the cardiac phenotype of a mouse model for myotonic dystrophy, type 1. J. Clin. Invest. (In Press).
Kuyumcu-Martinez , N.M. , Wang, G.S., and Cooper, T.A. (2007) Increased steady state levels of CUG-BP1 in Myotonic Dystrophy 1 are due to PKC-mediated hyper-phosphorylation. Mol. Cell 28, 68-78.
Kuyumcu-Martinez NM, Cooper TA. (2006) Misregulation of alternative splicing causes pathogenesis in myotonic dystrophy. Prog Mol Subcell Biol. 44, 133-159.
Kuyumcu-Martinez, NM ., Joachims M., and Lloyd R.E. 2002. Efficient Cleavage of Ribosome-Associated Poly(A)-binding Protein by Enterovirus 3C protease. J.Virol. 2002 Mar; 76 (5):2062-2074.
Kuyumcu - Martinez , NM ., Van Eden Marc, and Lloyd R.E.2003. Cleavage of Poly(A)-Binding Protein By Poliovirus 3C Protease Inhibits Host Cell Translation: A Novel Mechanism for Host Translation Shutoff. Mol Cell Biol. 2004 Feb; 24 (4):1779-90.
Kuyumcu - Martinez , NM ., Belliot G, Sosnovtsev SV, Green KY and Lloyd R.E.2003. Calicivirus 3C protease inhibits cellular translation by cleaving poly(A)-binding protein by enterovirus 3C protease. J Virol. 2004 Aug; 78 (15):8172-82.
Graham KL., Gustin KE., Rivera C., Kuyumcu - Martinez, NM ., Choe SS., Lloyd RE., Sarnow P., Utz PJ. Proteolytic Cleavage of The Catalytic Subunit of DNA-dependent Protein Kinase During Poliovirus Infection. J Virol. 2004. Jun 78(12):6313-21.