Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin

Pradhan, Shalmali Avinash and Rather, Mohammad Iqbal and Tiwari, Ankana and Bhat, Vishwanath Kumble and Kumar, Arun (2014) Evidence that TSC2 acts as a transcription factor and binds to and represses the promoter of Epiregulin. In: NUCLEIC ACIDS RESEARCH, 42 (10). pp. 6243-6255.

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Abstract

The TSC2 gene, mutated in patients with tuberous sclerosis complex (TSC), encodes a 200 kDa protein TSC2 (tuberin). The importance of TSC2 in the regulation of cell growth and proliferation is irrefutable. TSC2 in complex with TSC1 negatively regulates the mTOR complex 1 (mTORC1) via RHEB in the PI3K-AKT-mTOR pathway and in turn regulates cell proliferation. It shows nuclear as well as cytoplasmic localization. However, its nuclear function remains elusive. In order to identify the nuclear function of TSC2, a whole-genome expression profiling of TSC2 overexpressing cells was performed, and the results showed differential regulation of 266 genes. Interestingly, transcription was found to be the most populated functional category. EREG (Epiregulin), a member of the epidermal growth factor family, was found to be the most downregulated gene in the microarray analysis. Previous reports have documented elevated levels of EREG in TSC lesions, making its regulatory aspects intriguing. Using the luciferase reporter, ChIP and EMSA techniques, we show that TSC2 binds to the EREG promoter between -352 bp and -303 bp and negatively regulates its expression. This is the first evidence for the role of TSC2 as a transcription factor and of TSC2 binding to the promoter of any gene.

Item Type:	Journal Article
Publication:	NUCLEIC ACIDS RESEARCH
Additional Information:	Copyright for this article belongs to the OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	27 Aug 2014 04:57
Last Modified:	27 Aug 2014 04:57
URI:	http://eprints.iisc.ac.in/id/eprint/49681

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