Affiliation:
1. Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences Indian Institute of Technology Madras Chennai Tamil Nadu India
Abstract
Calnuc (nucleobindin‐1, nucb1) is a Ca2+‐binding protein involved in the etiology of many human diseases. To understand the functions of calnuc, we have identified a nesfatin‐1‐like peptide (NLP) in its N terminus that is proteolyzed by a convertase enzyme in the secretory granules of cells. Mutational studies confirm the presence of a proteolytic cleavage site for proprotein convertase subtilisin/kexin type 1 (PCSK1). We demonstrate that NLP regulates Gαq‐mediated intracellular Ca2+ dynamics, likely via a G‐protein‐coupled receptor. NLP treatment to carcinoma cell lines (SCC131 cells) promotes the expression of regulators of cell cycle, proliferation, and clonogenicity by the AKT/mTOR pathway. NLP is causative of augmented migration and epithelial–mesenchymal transition (EMT), illustrating its metastatic propensity and establishing its tumor promotion ability.
Funder
Board of Research in Nuclear Sciences
Indian Institute of Technology Madras
Indian Council of Medical Research
Subject
Cell Biology,Genetics,Molecular Biology,Biochemistry,Structural Biology,Biophysics