Name: Priyanka Singh
Diploma / M.Sc degree: Jawaharlal Nehru University New Delhi, India
(June 2007)

PhD Project: Analysing the regulation of eukaryotic gene expression by tumor suppressor Pdcd4

Abstract of Research Project

The control of eukaryotic gene expression is dependent upon the assembly of specific protein-protein and protein-nucleic acid complexes in a dynamic and highly regulated process. The protein, programmed-cell-death-4, PDCD4 (also known as MA-3, TIS, H731, DUG) is a highly conserved eukaryotic protein, which plays a critical role in regulation of both transcription and translation. It was initially discovered while screening for the genes which are activated during apoptosis and then as tumor suppressor in a mouse keratinocyte model of tumor promotion.

Characterization of the cellular functions of PDCD4 is the focus of many ongoing investigations. However, recent work indicates essential roles of PDCD4 in the control of both transcription and translation, mediated via protein–protein and protein–RNA interactions. But, it is still not clear as to how PDCD4 exerts its effects as an inhibitor of translation. The protein is found to shuttle between the nucleus and the cytoplasm, depending on the growth conditions. These observations suggest, that in addition to its suspected role in translation, the Pdcd4 protein may have a role in the nucleus as well.

The objective of my research project is to analyse the regulation of eukaryotic gene expression by the tumor suppressor PDCD4 (Programmed cell death 4). It is currently thought that Pdcd4 inhibits the translation of specific RNAs through interaction with the translation initiation factors eIF4A and eIF4G. In this project I would like to further investigate the protein interactions of Pdcd4 in order to understand the mechanisms by which Pdcd4 regulates its translational targets.



Publications

L. Wedeken, P. Singh, K.-H. Klempnauer
Tumor Suppressor Protein Pdcd4 Inhibits Translation of p53 mRNA
J. Biol. Chem. 286 (2011), 42855-42862.

P. Singh, L. Wedeken, L. C. Waters, M. D. Carr, K.-H. Klempnauer
Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation
Oncogene 30 (2011), 4864–4873.

P. Singh, R. Marikkannu, N. Bitomsky, K.-H. Klempnauer
Disruption of the Pdcd4 tumor suppressor gene in chicken DT40 cells reveals its role in the DNA-damage response
Oncogene 28(42) (2009), 3758-3764.


Priyanka Singh
eMail: Priyanka Singh