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Research Interests

Choice of a cell to undergo differentiation, division, or cell death forms the basis of development and functioning of tissues in multi-cellular organisms. Our interest has been in understanding the molecular players that regulate gene expression and cytoskeletal remodelling to guide cells to achieve specialized properties and form functional tissues. How these molecules respond to extracellular cues and simultaneously regulate multiple properties of the cell spatially and temporally has been our challenge. Salient findings have been, identification of the guanine nucleotide exchange factor, RapGEF1 as a regulator of actin dynamics, differentiation, and survival. RapGEF1 functions as a suppressor of ?-catenin and regulates chromatin dynamics. We have shown novel mechanisms of c-Abl and Bcr-Abl regulation, and our work has provided leads to understanding control of cell fate, and reversing the malignant phenotype of some human cancers. Ongoing work explores the molecular mechanisms involved in regulation of proliferation vs. differentiation in cells during development, and maintenance of homeostasis in adult tissues. Using cells in culture, we model physiological differentiation, and use human disease associated mutants to understand pathophysiology.

Selected Publications

Sanjeev Chavan Nayak, Vegesna Radha* (2020). C3G localizes to the mother centriole dependent on cenexin, and regulates centrosome duplication and primary cilia length. Journal of Cell Science 133(11) jcs.243113 doi: 10.1242/jcs.243113.

Raghawan A K, Rajashree R, Radha V*, and Swarup G*. (2019) HSC70 regulates   cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4. Proc Natl Acad Sci, USA 116 (41), 20243-20244.

Dhruvkumar Shakyawar, Muralikrishna Bhattiprolu & Vegesna Radha* (2018) "C3G dynamically associates with nuclear speckles and regulates mRNA splicing". Mol Biol Cell 29(9):1111-1124.

Shakyawar DK, Dayma K, Ramadhas A, Varalakshmi C, Radha V*.(2017) C3G shows regulated nucleo-cytoplasmic exchange and represses histone modifications associated with euchromatin. Mol Biol Cell. 28: 984-995, 2017K.

Sasi Kumar, A. Ramadhas, S.C. Nayak, S. Kaniyappan,  K. Dayma, V.Radha*(2015) C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. BBA-Mol. Cell Res. 1853: 2629-2639.

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Publications

TitleJournalYear
C3G localizes to the mother centriole in a cenexin-dependent manner, and regulates centrosome duplication and primary cilia length. Journal of Cell Science jcs.243113 doi: 10.1242/jcs.243113. 2020
HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4. Proc Natl Acad Sci, USA 116 (41), 20243-20244. 2019
C3G dynamically associates with nuclear speckles and regulates mRNA splicing Mol Biol Cell 29(9):1111-1124 PMID:29496966 2018
Development and characterization of a novel monoclonal antibody that recognizes an epitope in the central protein interaction domain of RapGEF1 (C3G). Mol Biol Reports 2018 Aug 24. doi: 10.1007/s11033-018-4327-0. 2018
A disease-associated mutant of NLRC4 shows enhanced interaction with SUG1 leading to constitutive FADD dependent caspase-8 activation and cell death. J Biol Chem, 292(4):1218-1230. 2017
C3G. Encyclopedia of Signaling Molecules Springer Nature.Choi, Sangdun (Ed.) in Press.DOI 10.1007/978-1-4614-6438-9_101544- 2017
CDC20siRNA and paclitaxel co-loaded nanometric liposomes of nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma. Nanoscale; 9, 1201-1212. 2017
C3G shows regulated nucleo-cytoplasmic exchange and represses histone modifications associated with euchromatin. Mol Biol Cell. 28: 984-995, 2017 2017
661W is a retinal ganglionprecursor-like cell line in which glaucoma-associated optineurin mutants induce cell death selectively. Scientific Reports, 4;7(1):16855 2017
pH and Thermo-sensitive 5 Fluorouracil loaded Poly (Nipam-co-AAc) Nanogels for Cancer Therapy. RSC Advances; 6, 105495-105507 DOI: 10.1039/ C6RA18034E 2016
Use of dominant negative/substrate trapping PTP mutations to search for PTP interactors /substrates. Methods in Molecular Biology. 1447: 243-265. 2016
C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. BBA-Mol. Cell Res. Volume 1853, Issue 10, Part A, October 2015, Pages 2629-2639 2015
E50K-OPTN-induced retinal cell death involves the Rab GTPase-Activating Protein, TBC1D17 mediated block in autophagy. PLoS One, 9(4): e95758 2014
M98K-optineurin induces transferrin receptor degradation and Rab12-mediated autophagic death in retinal ganglion cells. Autophagy 9:510-527 2013
When a cell decides to die: multiple options. Proc. AP Acad. Sci. 15: 41-46 2013
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. Biochim Biophys Acta. Mol.Basis of Dis. 1832: 275-284. 2013
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. Biochim Biophys Acta. Mol.Basis of Dis. 1832: 275-284. 2013
Dynamic changes in nuclear localization of a DNA-binding protein tyrosine phosphatase TCPTP in response to DNA damage and replication arrest. Cell Biol Toxicol 28:409-419 2012
Reciprocal negative regulation between the guanine nucleotide exchange factor C3G and ?-catenin Genes & Cancer 3:564-577 2012
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. Biochim Biophys Acta 1832 (1): 275-284 2012
Lamins, laminopathies and disease mechanisms: Possible role for proteasomal degradation of key regulatory proteins J. Biosci., 36:471-479 2011
TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells. PLoS ONE 6(8): e23681 2011
Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells. BBA- Mol. Cell. Res. 1813: 456-465 2011
Signaling to actin: Role of C3G, a multitasking guanine nucleotide exchange factor. Bioscience Reports 31: 231-244 2011
RAPGEF1 (Rap guanine nucleotide exchange factor (GEF) Atlas Genet Cytogenet Oncol Haematol. 2010
-actin binding domain of c-Abl regulates localized phosphorylation of C3G: Role of C3G in c-Abl mediated cell death . Oncogene 29: 4528-4542 2010
Interaction with Sug1 enables Ipaf ubiquitination leading to caspase-8 activation and cell death. Biochem. J. 427: 91-104. 2010
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. BMC Cell Biol. 11: 4. 2010
In vivo radioprotection by 5-aminosalicylic acid. Mutation Research 650: 63-79. 2008
The guanine nucleotide exchange factor, C3G regulates differentiation and survival of human neuroblastoma cells. J. Neurochem. 107: 1424-1435. 2008
CASPASE-1 Atlas Genet Cytogenet. Oncol. Haematol. 2007
IPAF / NLRC4 Atlas Genet Cytogenet Oncol. Haematol. 2007
Regulation of p73 by Hck through kinase-dependent and independent mechanisms. BMC Molecular Biology 8: 45. 2007
C3G is required for c-Abl induced filopodia and its overexpression promotes filopodia formation. Exp. Cell Res. 313: 2476-2492. 2007
A glaucoma associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. IOVS 48: 1607-1614. 2007
Involvement of caspase-1 and its activator Ipaf upstream of mitochondrial events in apoptosis. FEBS J. 273: 2766-2778. 2006
Role of p73 in regulating human caspase-1 gene transcription induced by Ifn-g & cisplatin. J Biol. Chem.280: 36664-36673. 2005
Transcriptional control of caspase gene expression. PINSA 70:551-577. 2004
Caspase-1 activator Ipaf is a p53 inducible gene involved in apoptosis. Oncogene 24: 627-636. 2004
Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and SFKs localizes to the Golgi and subcortical actin cytoskeleton. BMC Cell Biol. 5: 31. 2004
Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic activity J. Biol. Chem. 278: 52188-52194. 2003
A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1 dependent apoptosis. Febs Letts. 532: 61-66. 2002
Induction of cytochrome c release and apoptosis by Hck-SH3 domain- mediated signalling requires caspase-3. Apoptosis 7: 195-207. 2002
Direct transcriptional activation of human caspase-1 by tumor suppressor p53. J. Biol. Chem. 276: 10585- 10588. 2001
A nuclear protein tyrosine phosphatase induces shortening of G1 phase and increase in c-Myc protein level. Exp. Cell Res. 265: 1-10. 2001
Nuclear Matrix : Methods of Preparation. Encyclopedia of Life Sciences p. 1-3 2001
PTP-S2, a nuclear tyrosine phosphatase is phosphorylated and excluded from condensed chromosomes during mitosis. J. Biosci. 25: 33-40. 2000
Induction of p53 dependent apoptosis upon overexpression of a nuclear PTPase. FEBS Letts. 453: 308-312. 1999
Nuclear protein tyrosine phosphatases and control of cell proliferation. Curr. Sci. 73: 418-429. 1997
Overexpression of a nuclear protein tyrosine phosphatase increases cell proliferation. FEBS Letts. 409: 33-36. 1997
Two splice variants of a tyrosine phosphatase differ in substrate specificity, DNA binding and subcellular location J. Biol. Chem. 271: 26755- 26761. 1996
Association of Lyn tyrosine kinase with the nuclear matrix and cell-cycle- dependent changes in matrix-associated tyrosine kinase activity. Eur. J. Biochem. 236: 352-359. 1996
Subcellular localization of a protein tyrosine phosphatase : Evidence for association with chromatin. Biochemical J. 299: 41-47. 1994
Stabilization of a protein tyrosine phosphatase mRNA upon mitogenic stimulation of T-lymphocytes Biochim. Biophys. Acta. 1216: 205. 1993
Binding of protein tyrosine phosphatase to DNA through the carboxy terminal non-catalytic domain. Biochemistry 32: 2194. 1993
Binding of protein tyrosine phosphatase to DNA through the carboxy terminal non-catalytic domain. Biochemistry 32: 2194. 1993
Protein tyrosine phosphatases as regulators of protein kinase activity. Curr. Sci. 62: 462-469. 1992
Identification of human disease genes based on their map position Human Applied Genetics’ ed. Reddy, P.P. and Swarna, M. p. 104. 1991
Genetic studies in higher animals : New strategies. Curr. Sci. 60: 556. 1991
Molecular cloning and expression of a protein tyrosine phosphatase showing homology with transcription factors Fos and Jun. FEBS Letts. 280: 65. 1991
Essential fatty acids and peptic ulcer disease. GUT 27: 914. 1987
Plasma lipoproteins and LCAT in chronic liver disease. Ind. J. Gast. 6: 197. 1987
Salivary IgA in peptic ulcer patients. Curr. Sci. 56: 603. 1987
The Genetics of Peptic Ulcer Disease. Trop Gast. 6: 132. 1985
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V Radha

Emeritus Scientist

2619

vradha@ccmb.res.in

Divya Sriram

Senior Research Fellow

2648

divyasriram10@ccmb.res.in

Shivaranjani C Moharir

Senior Research Fellow

2615

shivranjani@ccmb.res.in