Shengkan (Victor) Jin  Assistant Professor UMDNJ Department of Pharmacology Room 529 683 Hoes Lane West Piscataway. NJ 08854 (732) 235-4329/6197 FAX - 235-4073 jinsh@umdnj.edu

Tumor suppressor genes. programmed cell death. tumorigenesis

One challenge that we humans and other animals with long life spans face is the accumulation of somatic genetic mutations. With the right combination these mutations may change the normal cell growth control. leading to cancer development. Programmed Cell Death (PCD) is one strategy evolved in these species to deal with the problem. In normal cells the well being of the cell is rigidly monitored by various cellular surveillance mechanisms. Genotoxic stresses that could lead to genetic alterations. such as DNA damage. hypoxia and oncogene activation. alert the surveillance systems. In turn. the surveillance systems could initiate programmed cell death. Consequently the damaged cells are eliminated. which efficiently prevents further accumulation of mutations in these cells and thus prevents cancer development. The functions of some tumor suppressors. including p53. are partially mediated by their abilities to trigger programmed cell death. It is apparent that cancer cells have acquired capabilities to evade programmed cell death during tumorigenesis. Genetic alterations that affect programmed cell death and its regulation are commonly found in cancer cells.

There are two major forms of programmed cell death in mammalian cells. apoptosis or type I programmed cell death. and autophagy or type II programmed cell death. We are currently studying both types of programmed cell death. their effects on tumorigenesis. and the regulations of programmed cell death by tumor suppressor p53. Furthermore we are exploring the strategy of targeting the program cell death machinery and its regulatory network as an approach to target cancers.

Selected Publications

Zhang Y, Qi H, Taylor R, Xu W, Liu LF, Jin S. (2007) The role of autophagy in mitochondria maintenance: Characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains. Autophagy. 9:3(4)

Shengkan J* and White, E. (2007) Role of autophagy in cancer: Management of metabolic stress. Autophagy 3 (1):28-31 (* SJ is a Co- corresponding author)

Jin S, Dipaola RS, Mathew R, White E. (2007). Metabolic catastrophe as a means to cancer cell death. J Cell Sci.120:379-83.

Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ. (2007) The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 67(7):3043-53.

Hars, ES, Qi, H, Jin, S, Cai, L, Hu, C and Liu, L. (2007). Autophagy regulates ageing in C. elegans. Autophagy. 3(2):93-5.

Jin, S. (2006) Autophagy, mitochondria quality control, and oncogenesis. Autophagy. 2(2): 80-84.

Degenhardt, K., Mathew, R., Beaudoin, B., Bray, K., Anderson, D, Chen, G., Mukherjee, C., Shi, Y., Nelson, D.A., Jin, S., and White, E. (2006). Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 10(1):51-64.

Hait WN. Jin S. Yang JM. (2006) A matter of life or death (or both): understanding autophagy in cancer. Clin Cancer Res. 12(7 Pt 1):1961-5.

Wu H. Yang JM. Jin S. Zhang H. Hait WN. (2006) Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Res. 66(6):3015-23.

Levine AJ. Feng Z. Mak TW. You H. Jin S. (2006) Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 20(3):267-75.

Jin. S. (2005) p53. autophagy. and tumor suppression. Autophagy. 1 (3). 34-36.

Feng Z. Zhang H. Levine AJ. Jin S. (2005) The coordinate regulation of the p53 and mTOR pathways in cells.Proc Natl Acad Sci. 102(23):8204-9.

Yue. Z. Jin. S. Yang. C. Levine. AJ. Heintz. N. (2003). Beclin1. an autophagy gene essential for early embryo development. is a tumor suppressor. Proc. Nat. Acad. Sci. 100 (25): 15077-15082.

Jin. S. Kalkum. M. Overholtzer. M. Stoffel. A. Chait. BT and Levine. AJ (2003) CIAP1 and the serine protease HTRA2 are involved in a novel p53-dependent apoptotic Pathway in mammals. Genes and Development 17:359-367.

Hoh. J. Jin*. S.. Parrado. T. . Edington. J. . Levine. AJ . Ott. J. (*S. Jin is a co-first author). (2002) The p53MH algorithm and its application in detecting p53-responsive genes. Proc. Nat. Acad. Sci. 99 (13): 8467-8472.

Jin. S and Levine. A.J. (2001) p53 function circuit. Journal of Cell Science 114 ( 23): 4139-40.

Jin. S. Martinek. S. Wortman. JR. Joo. WS. Mirkovic. N. Sali. A. Pavletich. NP. Yandell. MD. Young. MW and Levine. AJ. (2000) Identification and characterization of a p53 homologue in Drosophila melanogaster. Proc. Nat. Acad. Sci. Vol. 97 (13): 7301-7306.

Jin. S. Gorfajn. B. Faircloth. G and Scotto. KW. (2000) Ecteinascidin 743. an antitumor agent with novel mechanism. inhibits the transcriptional activation of the MDR1gene. Proc. Nat. Acad. Sci. Vol. 97 (12): 6775-6779.

Hu. Z. Jin. S and Scotto. KW. (2000) Transcriptional activation of the MDR1 gene by UV irradiation: Role of NF-Y and SP1. Journal of Biological Chemistry. Vol. 275(4): 2979-2985.