Venezia by PVII

Ning-Hui Cheng, Ph.D. Ning-Hui Cheng, Ph.D.

Instructor of Pediatrics
Baylor College of Medicine
ncheng@bcm.tmc.edu

Redox regulation of insulin signaling in nutrient metabolism

My research interests center on studying redox regulation of insulin signaling in nutrient metabolism with emphasis on metabolic disorders including type2 diabetes and obesity.

Redox regulation incorporates both transcriptional and post-translational mechanisms to modulate gene expression and protein levels. Thiol group modification represents one of redox control mechanisms in insulin action and signaling. There is growing evidence that the glutaredoxin (Grx)/ glutathione (GSH)/ glutathione reductase (GR) system, like the thioredoxin (Trx)/thioredoxin reductase (TR)/NADPH system,  plays an essential role in regulating cellular function. It will be important to understand the mechanistic link between Grx-mediated redox signals and insulin signaling pathways and the biochemical nature of those processes.

As an initial step towards this goal, we are currently investigating a novel group of Grxs-monothiol Grxs, which were recently identified and isolated from bacteria, fungi, plants, and animals including mammals. Recent studies from ours and other laboratories indicate that monothiol Grxs contain a conserved PICOT-HD (protein kinase C interacting cousin of thioredoxin homology domain) and have a common function in regulating cellular processes in response to oxidative stresses. By utilizing genetic, biochemical, and cell biology approaches, we are going to determine a), the biochemical properties of those enzymes including their enzymatic activities and substrate specificity; b), how these monothiol Grxs, coupled with GSH and GR, regulate the targeted proteins in response to cellular redox changes; and c), how the PICOT-HD integrates redox signals into insulin/IGF mediated signaling. Elucidating the physiological role of PICOT will lead to an understanding of the complexity of insulin resistance in the pathogenesis of metabolic disorders, such as type2 diabetes and obesity.

Representative publications:

Cheng, N.-H.* (2008) AtGRX4, an Arabidopsis chloroplastic monothiol glutaredoxin, is able to suppress yeast grx5 mutant phenotypes and respond to external stresses. FEBS Letters. 582, 848-854   (* Denotes Corresponding Author)

Koren’kov, V., Park, S., Cheng, N.-H., Sreevidya, C., Lachmansingh, J., Morris, J., Hirschi, K., Wagner, G.J. (2007) Enhanced Cd2+-selective root-tonoplast-transport in tobacco expression Arabidopsis cation exchangers. Planta 255, 403-411, 2007.

Cheng, N-H.*, Liu, Z-J., Brock, A., Nelson, R.S., and Hirschi, K.D. AtGRXcp, an Arabidopsis chloroplastic glutaredoxin is critical for protection against protein oxidative damage. J. Biol. Chem. 281, 26280-26288, 2006.

Park S, Cheng N-H, Pittman JK, Yoo KS, Park J, Smith RH, Hirschi KD. Increased calcium levels and prolonged shelf life in tomatoes expressing Arabidopsis H+/Ca2+ transporters. Plant Physiol. 139(3):1194-1206, 2005.

Cheng N-H, Pittman JK, Shigaki T, Lachmansingh J, LeClere S, Lahner B, Salt DE, Hirschi KD. Functional association of Arabidopsis CAX1 and CAX3 is required for normal growth and ion homeostasis. Plant Physiol. 138(4):2048-2060, 2005.

Pittman JK, Shigaki T, Marshall JL, Morris JL, Cheng N-H, Hirschi KD. Functional and regulatory analysis of the Arabidopsis thaliana CAX2 cation transporter. Plant Mol Biol. 56(6):959-971, 2004.

Ding X, Liu J, Cheng N-H, Folimonov A, Hou Y, Bao Y, Katagi C, Carter S, and Nelson R (2004) The Tobacco mosaic virus 126-kDa protein associated with virus replication and movement suppresses RNA silencing. Mol.Plant-Microbe Interact. 17, 583-592.

Yang S, Carter S, Cole A, Cheng N-H, and Nelson R (2004) A natural variant of a host RNA-dependent RNA polymerase is associated with increased susceptibility to viruses by Nicotiana benthamiana. Proc. Natl. Acad. Sci. USA 101, 6297-6302

Sze H, Padmanaban S, Cellier F, Honys D, Cheng N-H, Bock K, Conejero G, Li X, Twell D, Ward JM, and Hirschi K (2004). Expression Patterns of a Novel AtCHX Gene Family Highlight Potential Roles in Osmotic Adjustment and K1 Homeostasis in Pollen Development. Plant Physiol. 136:2532-2547.

Pittman J, Cheng N-H, Shigaki T, Kunta M, Hirschi K (2004). Functional dependence on calcineurin by variants of the Saccharomyces cerevisiae vacuolar Ca2+/H+ exchanger Vcx1p. Molecular Microbiology 54 (4), 1104–1116.

Cheng N-H*, Liu J, Nelson S, Hirschi K (2004). Characterization of CXIP4, a novel Arabidopsis protein that activates the H+/Ca2+ antiporter, CAX1. FEBS Letters. 559: 99-106.

Cheng N-H, Pittman J K, Zhu K, and Hirschi K (2004). The Protein Kinase SOS2 Activates the Arabidopsis H+/Ca2+ Antiporter CAX1 to Integrate Calcium Transport and Salt Tolerance. J. Biol. Chem. 279: 2922-2926.

Cheng N-H and Hirschi K (2003). Cloning and Characterization of CXIP1, a Novel PICOT Domain-containing Arabidopsis Protein That Associates with CAX1. J. Biol. Chem. 278: 6503 - 6509.

Cheng N-H, Pittman J K, Barkla B,  Shigaki T, and Hirschi K (2003). The Arabidopsis cax1 Mutant Exhibits Impaired Ion Homeostasis, Development, and Hormonal Responses and Reveals Interplay among Vacuolar Transporters. Plant Cell 2003 15: 347-364.

Cheng, N-H, Pittman, JK, Shigaki, T, and Hirschi, KD, (2002) Characterization of CAX4, an Arabidopsis H+/Cation antiporter. Plant Phsiol. 128:1245-1254

Pittman, JK, Shigaki, T, Cheng, N-H, and Hirschi, KD, (2002) Mechanism of N-terminal autoinhibition in the Arabidopsis Ca2+ /H+ antiporter CAX1. J Biol Chem 277, 26452-26459

Li XB, Cai L, Cheng,N-H, and Liu JW. (2002) Molecular characterization of the cotton GhTUB1 gene that is preferentially expressed in fiber. Plant Physiol. 130(2): 666-74.

Shigaki, T, Cheng, N-H, Pittman, JK, and  Hirschi, KD.  (2001)  Structural determinants of Ca 2+ transport in the Arabidopsis H+/Ca2+ antiporter CAX1.  J Biol. Chem 276: 43152-43159

Cheng, N-H, Su, C-L, Carter, SA, and Nelson, RS.  (2000). Vascular invasion routes and accumulation pattern of tobacco mosaic virus in Nicotiana;benthamiana; The Plant Journal. 23: 349-363