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Front Mol Biosci. 2014 Jul 25;1:6. doi: 10.3389/fmolb.2014.00006. eCollection 2014.

Wrecked regulation of intrinsically disordered proteins in diseases: pathogenicity of deregulated regulators.

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1
Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida Tampa, FL, USA ; Biology Department, Faculty of Science, King Abdulaziz University Jeddah, Saudi Arabia ; Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences Moscow, Russia.

Abstract

Biologically active proteins without stable tertiary structure are common in all known proteomes. Functions of these intrinsically disordered proteins (IDPs) are typically related to regulation, signaling, and control. Cellular levels of these important regulators are tightly regulated by a variety mechanisms ranging from firmly controlled expression to precisely targeted degradation. Functions of IDPs are controlled by binding to specific partners, alternative splicing, and posttranslational modifications among other means. In the norm, right amounts of precisely activated IDPs have to be present in right time at right places. Wrecked regulation brings havoc to the ordered world of disordered proteins, leading to protein misfolding, misidentification, and missignaling that give rise to numerous human diseases, such as cancer, cardiovascular disease, neurodegenerative diseases, and diabetes. Among factors inducing pathogenic transformations of IDPs are various cellular mechanisms, such as chromosomal translocations, damaged splicing, altered expression, frustrated posttranslational modifications, aberrant proteolytic degradation, and defective trafficking. This review presents some of the aspects of deregulated regulation of IDPs leading to human diseases.

KEYWORDS:

alternative splicing; conformational diseases; expression; intrinsically disordered proteins; posttranslational modification; proteolytic degradation; trafficking; transcriptional activation

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