IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells

Kalita, Anjana and Gupta, Sakshi and Singh, Preeti and Surolia, Avadhesha and Banerjee, Kakoli (2013) IGF-1 stimulated upregulation of cyclin D1 is mediated via STAT5 signaling pathway in neuronal cells. In: IUBMB Life, 65 (5). pp. 462-471.

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Abstract

Signal Transducer and Activator of Transcription (STATs) regulate various target genes such as cyclin D1, MYC, and BCL2 in nonneuronal cells which contribute towards progression as well as prevention of apoptosis and are involved in differentiation and cell survival. However, in neuronal cells, the role of STATs in the activation and regulation of these target genes and their signaling pathways are still not well established. In this study, a robust cyclin D1 expression was observed following IGF-1 stimulation in SY5Y cells as well as neurospheres. JAK/STAT pathway was shown to be involved in this upregulation. A detailed promoter analysis revealed that the specific STAT involved was STAT5, which acted as a positive regulatory element for cyclin D1 expression. Overexpression studies confirmed increase in cyclin D1 expression in response to STAT5a and STAT5b constructs when compared to dominant-negative STAT5. siRNA targeting STAT5, diminished the cyclin D1 expression, further confirming that STAT5 specifically regulated cyclin D1 in neuronal cells. Together, these findings shed new light on the mechanism of IGF-1 mediated upregulation of cyclin D1 expression in neural cell lines as well as in neural stem cells via the JAK/STAT5 signaling cascade.

Item Type:	Journal Article
Publication:	IUBMB Life
Publisher:	Wiley-Blackwell
Additional Information:	Copyright of this article belongs to Wiley-Blackwell.
Keywords:	STAT5; JAK/STAT; CCND1; Neuronal; IGF-1
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	11 Jun 2013 07:52
Last Modified:	11 Jun 2013 07:52
URI:	http://eprints.iisc.ac.in/id/eprint/46640

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