Faculty

Biochemistry and Molecular Genetics Faculty.

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Contact Information

University Of Illinois at Chicago

Dept. Of Biochemistry and

Molecular Genetics

900 S. Ashland (M/C 669)
Chicago, IL 60607
tel: 312-996-7670
fax: 312-413-0353

Dr. Pradip Raychaudhuri

pradip@uic.edu

Major Interests:

Cell cycle regulation by the tumor suppressor proteins and regulatory properties of the E2F family of transcription factors. Mechanisms that control DNA replication in mammalian cells are critical targets of oncogenic pathways. The main difference between normal and tumor cells is in their ability to control DNA replication and cell division. In normal cells, DNA replication is tightly controlled by the levels of several proteins and enzymes that are essential to carry out DNA synthesis. These replication proteins and enzymes are expressed in much higher levels by the tumor cells. We study the E2F-family of transcription factors (E2Fs) because they play a central role in regulating transcription of several cell cycle-regulated replication genes, including the cyclins. E2Fs are also targets of DNA virus oncoproteins and cellular tumor suppressors. E2Fs form repressor complexes with the Rb-family proteins to reduce expression of the replication genes in resting cells and in terminally differentiated cells. We have shown that many growth inhibitors (such as p53, p21Cip1, and p27Kip1) inhibit cell growth by ultimately generating the repressor forms of E2Fs, which shut off expression of the replication genes.


Dr. Pradip Raychaudhuri, Professor PhD, Albert Einstein College of Medicine Postdoctoral, Duke University

The scenario is the opposite in dividing cells and in tumor cells where E2Fs are present mainly in their activator forms and they stimulate expression of the replication genes.
The current focus of my lab is to characterize the transcriptional activation partners of E2Fs and evaluate their role in tumorigenesis. We are studying E2F1 because it has been shown to be critical for tumor cell division in mice. Moreover, most human tumor cell lines overexpress E2F1. We have shown that DDB can function as an activation partner of E2F1. We have generated a knockout strain of mice lacking expression of the small subunit (DDB2) of DDB. We find that these mice are deficient in DNA repair, and they are highly susceptible to carcinogenesis. We are investigating the mechanism that leads to tumor development in DDB2 -/- mice.
We are also studying the tumor suppressor ARF, which is mutated or inactivated in a wide variety of tumors. Our studies indicate that the E2F family of transcription factors E2F1 and DP1 are targets of ARF. We showed that ARF could inhibit E2F-activated transcription by inducing proteolysis of E2F1 and DP1. We are currently in the process of evaluating the significance of the E2F-regulatory function in the tumor suppression function of ARF.

Selected Publications:

Wang J, Sampath A, Raychaudhuri P, Bagchi S. 2001. Both Rb and E7 are regulated by the ubiquitin proteasome pathway in HPV-containing cervical tumor cells. Oncogene. 20:4740-9.

Lee, M-H., Mori, S. and Raychaudhuri, P. (1996): Trans-activation by the hnRNP protein involves an increase in RNA synthesis from the reporter genes. J. Biol. Chem. 271, 3420-3427.

Shiyanov, P., Bagchi, S., Adami, G.R., Kokontis, J., Hay, N., Morosov, A. and Raychaudhuri, P. (1996): p21 disrupts the interaction between cdk2 and the E2F/p130 complex. Mol. Cell. Biol. 16, 737-744.

Shiyanov, P., Hayes, S., Chen, N., Pestov, D.G., Lau, L.F. and Raychaudhuri, P. (1997): p27 Kip1 induces an accumulation of the repressor complexes of E2F and inhibits expression of the E2F-regulated genes. Mol. Biol. Cell. (in press, September issue).

Nag A, Datta A, Yoo K, Bhattacharyya D, Chakrabortty A, Wang X, Slagle BL, Costa RH, Raychaudhuri P. 2001. DDB2 induces nuclear accumulation of the hepatitis B virus X protein independently of binding to DDB1. J Virol. 75:10383-92.

Nag A, Bondar T, Shiv S, Raychaudhuri P. 2001. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Mol Cell Biol. 21:6738-47.

Wang J, Sampath A, Raychaudhuri P, Bagchi S. 2001. Both Rb and E7 are regulated by the ubiquitin proteasome pathway in HPV-containing cervical tumor cells. Oncogene. 20:4740-9.

Datta A, Nag A, Raychaudhuri P. 2002., Differential Regulation of E2F1, DP1, and the E2F1/DP1 Complex by ARF. Mol Cell Biol. 22:8398-408.