The Department of Molecular and Cellular Biochemistry




Sung Ok Yoon

Associate Professor

Ph.D. - Tufts University Medical School

Post Doctoral - Cornell University Medical School

Project 1: One of the current focuses of the lab is to understand the signaling mechanisms by NGF, which can promote either neuronal survival or death, depending on the outcome of the interplay between its two distinct receptors, TrkA, a receptor tyrosine kinase, and p75, a member of the TNF receptor family. We have recently determined that p75 activates Rac GTPase upon binding NGF, which is in turn required for activation of c-jun N-terminal kinase and subsequent apoptosis. Co-activation of TrkA and 75 results in attenuation of Rac activity, suggesting that Rac is a critical component in determination of cell survival and death. We now have identified a Rho family of guanidine exchange factor that binds p75, and we will focus on biochemical understanding of its regulation by NGF.

Project 2: p75 is often induced after various insults and injuries in vivo.  Using spinal cord injury as a model, we have recently determined that p75 activation is a critical component in apoptosis in vivo. Both in the spinal cord and in the brain, p75 is activated by pro-NGF, a precursor form of NGF, which binds p75 selectively, and not TrkA. We are currently investigating the signaling mechanisms by which pro-NGF activates p75 in vivo using spinal cord injury and cortical spinal axotomy as models.

 

Recent Publications:
Li QM, Tep C, Yune TY, Zhou XZ, Uchida T, Lu KP, Yoon SO (2007) “Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury” J Neurosci. 27(31):8395-404

Massa SM, Xie Y, Yang T, Harrington AW, Kim ML, Yoon SO and Kraemer R (2006) "Small, Nonpeptide p75NTR Ligands Induce Survival Signaling and Inhibit proNGF-induced Death" J Neurosci 26:5288-30

Beffert U, Nematollah-Farsian F, Masiulis I, Hammer R, Yoon SO, Herz J and Giehl KM (2006) "ApoE receptor 2 controls neuronal survival in the adult brain" Curr Biol 16:2446-2452.

Linggi MS, Burke TL, Williams BB, Harrington A, Karemer R, Hempstead BL, Yoon SO and Carter BD (2005) "NRIF is an essential mediator of apoptotic signaling by the p75 neurotrophin" J Biol Chem 280(14):13801-08.

Bai S, Ghoshal K, Datta J, Majumder S, Yoon SO and Jacob ST (2005) "DNA methyltransferase 3b regulates NGF-induced differentiation of PC12 cells by recruiting histone deacetylase 2" Mol Cell Biol 25(2):751-66.

Guibin L, Faibuschevich A, Turunen BJ, Yoon SO, Georg G, Michaelis ML and Dobrowsky RT (2003) "Stabilization of the cyclin-dependent kinase 5 activator, p35, by paclitaxel decreases ß-amyloid toxicity in cortical neurons" J Neurochem 84:347-62.

Tan W, Rouen S, Barkus KM, Dremina YS, Hui DW, Yoon SO and Dobrowsky RT (2003) "Nerve growth factor blocks the glucose-induced downregulation of caveolin-1 expression in schwann cells via p75 neurotrophin receptor signaling" J Biol Chem 278:23151-62.

Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM, Bresnahan JC, Hempstead BL and Yoon SO (2002) "Pro-NGF induces p75-mediated death of oligodendrocytes following spinal cord injury" Neuron 36:375-86.

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Last Modified: 10/10/07