Jian Kuang, Ph.D.

The central theme of my research is to understand the molecular mechanisms that control cell proliferation. We utilize molecular and biochemical approaches to attack this cellular problem. One of our major research projects is in the area of basic cell-cycle regulation and is designed to define the role of phosphorylation of the MPM-2 epitope in mitotic regulation. MPM-2 is a widely used monoclonal antibody that recognizes a specific protein epitope (FTPLQ) in a phosphorylation-dependent manner. Since phosphorylation of the MPM-2 epitope on many proteins during the G2/M transition is a universal cell-cycle event, the kinase and phosphatase that determine the phosphorylation status of the epitope are likely to be crucial cell-cycle regulators. We have been using biochemical approaches to identify these enzymes.

Another main project in my laboratory to understand the signaling mechanisms that control entry into or exit from the cell cycle. This project concerns identifying and characterizing p95^AIP1, a novel signal transduction protein that regulates cell proliferation, cell transformation, and apoptosis. We have demonstrated that Xenopus p95 is a substrate of the Src tyrosine kinase and undergoes phosphorylation during progesterone-induced oocyte maturation. Thus, we are currently using the Xenopus oocyte as the experimental system in which to dissect the p95-mediated signal transduction pathway. We have also discovered that overexpressing human p95 inhibits the transformation phenotype of highly malignant HeLa cells but has no general inhibitory effects on cell proliferation. We are currently investigating the mechanism by which overexpression of p95 achieves these effects.

The third component of my research the institution is in the area of cell-cycle checkpoint controls and currently addresses the molecular basis for the differential effects of 2 related DNA-damaging agents, cisplatin and DACH-acetato-Pt, on cell-cycle checkpoints of ovarian cancer cells. DACH-acetato-Pt is an analogue of cisplatin but is effective against cisplatin-resistant ovarian cancer cells. Understanding the differential effects of these 2 drugs on cell-cycle checkpoints may contribute to our understanding of their differential therapeutic effects.

Recent publications

He G, Siddik ZH, Koomen J, Kobayashi R, Huang Z, Khokhar K, Kuang J (2005) Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities. Oncogene 24:2929–43
Wu Y, Pan S, Che S, He G, Nelman-Gonzalez M, Weil MM, Kuang J (2001) Overexpression of Hp95 induces G1 phase arrest in confluent HeLa cells. Differentiation 67:135–153.
Che S, El-Hodiri HM, Wu CF, Nelman-Gonzalez M, Weil MM, Etkin LD, Clark RB, Kuang J (1999) Identification and cloning of xp95, a putative signal transduction protein in Xenopus oocytes. J Biol Chem 274:5522–5531.
Che, S., Wu, W., Nelman-Gonzalez, M., Stukenberg, T., Clark, R., and Kuang, J. (1998) A phosphatase activity in Xenopus oocyte extracts dephosphorylates the MPM-2 epitope. FEBS Lett 424:225–233.
Che, S., Weil, M. M., Nelman-Gonzalez, M., Ashorn, C. L., and Kuang, J. (1997) MPM-2 epitope sequence is not sufficient for recognition and phosphorylation by ME kinase-H. FEBS Letters, 413:417–423.
Kuang, J., and C. L. Ashorn. (1993) At least two kinases phosphorylate the MPM-2 epitope during Xenopus oocyte maturation. J Cell Biol. 123:859–868.
Kuang J, Zhao JY, Wright DA, Saunders GF, Rao PN (1989) Mitosis-specific monoclonal antibody MPM-2 inhibits Xenopus oocyte maturation and depletes maturation-promoting activity. Proc Natl Acad Sci USA 86:4982–4986.