title: Role of post translational modifications and novel crosstalk between phosphorylation and O-beta-GlcNAc modifications in human claudin-1, -3 and -4.
abstract: The precise characterization of post translational modifications (PTMs) is important for the understanding of protein regulatory mechanisms and their role in disease. However, experimental studies on PTMs, especially with multifunctional proteins are difficult to follow and investigate. Bioinformatic tools are therefore helpful in predicting key protein modifications. To study the role of PTMs in claudin proteins, specifically claudin-1, -3 and -4 in the onset or progression of human cancers, we performed an in silico study of various PTMs and investigated their interplay. Given that the activity of claudins is known to be influenced by two types of PTMs, specifically palmitoylation and kinase- dependent phosphorylation, we predicted two conserved regions in the topological domains of claudin-1, -3 and -4 as potential palmitoylation sites. Furthermore, conserved phosphorylation residues, which may be targets for kinases and can alter claudin's ability to maintain the integrity of tight junctions, were identified. To our knowledge, this is the first report to suggest O-glycosylation of claudin proteins, as well as a potential novel interplay between phosphorylation and O-glycosylation at Yin Yang sites. Thus, our findings may facilitate the production of anti-cancer drugs, and suggest that novel therapeutic strategies should target post translational events.
authors: National Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan. azeem@cemb.edu.pk
authors: Azeem Mehmood
authors: AM
authors: Butt
authors: Ishaque Badshah
authors: IB
authors: Khan
authors: Mureed
authors: M
authors: Hussain
authors: Muhammad
authors: M
authors: Idress
authors: Jun
authors: J
authors: Lu
authors: Yigang
authors: Y
authors: Tong
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