1. Research/Work Experience
1. (Feb, 2011 – November, 2013)
CCMB is a premier research institute in India in the field of cellular & molecular biology.
Studies on the role of signaling pathways involving C3G in cellular plasticity, with
Dr.V.Radha, in Centre for Cellular & Molecular Biology, Hyderabad, India.
C3G is a ubiquitous GEF molecule, which activates small GTPases and is triggered by
various signals in pathways. It’s a multi-functional molecule performing both catalytic
and non-catalytic functions.
• One of the objectives of my work deals with analyzing the role of C3G protein in nuclear
shuttling and checking the localization and behavior of C3G protein in the cytoplasm and
nucleus with various interacting partners. In this work so far, I have observed that C3G
localizes to the nucleus in 30% of normal cells. The nuclear localization pattern of C3G
increases upon inhibition of GSK3β, a negative regulator of β-catenin. C3G partly co-
localizes with euchromatin but is excluded from heterochromatin regions, indicating that
nuclear matrix might play a role in its localization. These observations indicated the role
of C3G in nuclear membrane organization and cytoskeletal rearrangements.
• Another objective of my work involves studying the role of C3G in muscle differentiation
in C2C12 cells. In this work so far, I have observed that endogenous level of C3G
increases during differentiation and over-expression of C3G shows complete
differentiation with elongated tubes. The cells differentiate upon culturing in a
differentiation medium, with an increase in level of myosin, a differentiation marker. This
study indicates the involvement of C3G in differentiation of C2C12 cells.
My other works from this lab have been published.
Publications
1. Reciprocal Negative Regulation between the Guanine Nucleotide Exchange Factor C3G
and β-Catenin. Dayma K, Ramadhas A, Sasikumar K, Radha V. Genes Cancer. 2012.
PMID: 23486661. (IF:4.41)
The guanine nucleotide exchange factor (GEF), C3G (RAPGEF1) regulates
proliferation, migration and differentiation of cells and is essential for mammalian embryonic
development. Our results identify a novel property of C3G in functioning as a negative
regulator of β-catenin signaling by promoting its degradation. In addition, we show that β-
catenin inhibits C3G expression, forming a feedback loop. Also C3G exerts its effect on β-
catenin independent of GSK3β. We suggest that alternate mechanisms are engaged by C3G to
cause β-catenin turnover, not by proteasome.
2. Dynamic changes in nuclear localization of a DNA binding protein tyrosine phosphatase
TCPTP in response to DNA damage and replication arrest. Sree NK, Anesh R and Radha
V. Cell Biology & Toxicology, 2012. PMID: 22976903. (IF:2.511)
TCPTP is ubiquitously expressed tyrosine phosphate with a prominent nuclear isoform
(TC45) that binds DNA and has a role in G1-S cell cycle progression. Our data suggests that
TCPTP is mobilized for a function required during DNA damage response and replication
stress. The DNA binding property and dynamic spatial distribution of TC45 are consistent
with its role as a modulator of cell cycle with particular functions in DNA replication and
repair.