Abstract

The major objective of this new proposal is to elucidate the role of cullin-4A in tumor development. This proposal is based on the interesting preliminary observations by the PI on the binding of cullin-4A with damaged-DNA recognition factor (DDB) in cell culture studies. To examine the role of cullin-4A in tumor development, the PI has hypothesized several mechanistic possibilities that will explain how overexpression of cullin-4A leads to the development of malignant tumors. The proposed studies will establish, 1) how cullin-4A modulates the functions of DDB; 2) how cullin-4A target DDB and cullin-4A are functionally different from cullin-4B; and 3) whether cullin-4A would be the target of any oncogenic pathways or whether it would cooperate with other oncogenes to immortalize or transform cells in culture. Also, the PI will develop a transgenic mouse model that over expresses cullin-4A in keratinocytes, which would enable him to study the oncogenic function in vivo.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA088863-02
Application #
6498062
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Blair, Donald G
Project Start
2001-02-01
Project End
2006-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$227,603
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Biochemistry
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Bondar, Tanya; Kalinina, Anna; Khair, Lyne et al. (2006) Cul4A and DDB1 associate with Skp2 to target p27Kip1 for proteolysis involving the COP9 signalosome. Mol Cell Biol 26:2531-9
Yoon, Taewon; Chakrabortty, Amit; Franks, Roberta et al. (2005) Tumor-prone phenotype of the DDB2-deficient mice. Oncogene 24:469-78
Rajabi, Hasan N; Baluchamy, Sudhakar; Kolli, Sivanagarani et al. (2005) Effects of depletion of CREB-binding protein on c-Myc regulation and cell cycle G1-S transition. J Biol Chem 280:361-74
Datta, Abhishek; Nag, Alo; Pan, Wei et al. (2004) Myc-ARF (alternate reading frame) interaction inhibits the functions of Myc. J Biol Chem 279:36698-707
Bondar, Tanya; Ponomarev, Aleksandr; Raychaudhuri, Pradip (2004) Ddb1 is required for the proteolysis of the Schizosaccharomyces pombe replication inhibitor Spd1 during S phase and after DNA damage. J Biol Chem 279:9937-43
Nag, Alo; Bagchi, Srilata; Raychaudhuri, Pradip (2004) Cul4A physically associates with MDM2 and participates in the proteolysis of p53. Cancer Res 64:8152-5
Bondar, Tanya; Mirkin, Ekaterina V; Ucker, David S et al. (2003) Schizosaccharomyces pombe Ddb1 is functionally linked to the replication checkpoint pathway. J Biol Chem 278:37006-14
Nag, A; Bondar, T; Shiv, S et al. (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