Regulation of Hormone and Growth factor Signalling by Ubiquitin and Ubiquitin-like Protein Modifications

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Background

Body functions, including growth and development, metabolism, electrolyte balances, and reproduction, rely on the signals generated by hormones and their receptors in target cells. While the key biochemical pathways involved in hormonal cascades have been mapped, studies in the recent decade have revealed the importance of ubiquitin and ubiquitin-like proteins in fine-tuning signal transduction and receptor trafficking. Ubiquitination, a post-translational modification that was originally discovered in the context of protein degradation and protein quality control has been accorded novel roles in endocytosis of membrane receptors, signal propagation, and signal compartmentalization, thus regulating hormonal responses in target cells. Endocytosis and lysosomal trafficking of growth hormone, adrenergic, and parathyroid hormone receptors are orchestrated by ubiquitination of the respective membrane receptors. Additionally, while insulin and glucagon-induced endocytic trafficking also involves ubiquitination, studies have also shown that the ubiquitin-like modification, called SUMOylation regulates glucose-induced insulin secretion in pancreatic beta cells. Aside from the impact on specific receptor and associated molecules and their intracellular trafficking, it is very likely that ubiquitin-dependent mechanisms play a more global role in mediating hormonal control of cellular homeostasis.

In this review series, the novel functions of ubiquitin and ubiquitin-like proteins in the regulation of hormone-induced signal transduction will be highlighted and their importance in therapeutic targeting will be discussed. This article collection will serve as a major reference point for investigators to obtain a perspective on the current understanding of the field and encourage further technological and mechanistic advances in this field.

We are particularly interested, but not limited to, to the following themes:
• Ubiquitination and Hormone-induced trafficking
• Novel roles for ubiquitination in signal transduction
• Ubiquitination and metabolic disorders

Keywords: E3 ubiquitin ligases, deubiquitinases, protein degradation, protein trafficking, metabolic disorders

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