Journal
BIOESSAYS
Volume 40, Issue 5, Pages -Publisher
WILEY
DOI: 10.1002/bies.201700223
Keywords
aging; CHIP; diabetes; DUBs; E3 ligase; insulin signaling; oncogenesis; proteostasis; ubiquitin
Categories
Funding
- European Research Council [616499]
- National Science Centre, Poland [UMO-2016/23/B/NZ3/00753]
- European Research Council (ERC) [616499] Funding Source: European Research Council (ERC)
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The insulin/insulin-like growth factor-1 (IGF-1) signaling (IIS) pathway is a pivotal genetic program regulating cell growth, tissue development, metabolic physiology, and longevity of multicellular organisms. IIS integrates a fine-tuned cascade of signaling events induced by insulin/IGF-1, which is precisely controlled by post-translational modifications. The ubiquitin/proteasome-system (UPS) influences the functionality of IIS through inducible ubiquitylation pathways that regulate internalization of the insulin/IGF-1 receptor, the stability of downstream insulin/IGF-1 signaling targets, and activity of nuclear receptors for control of gene expression. An age-related decline in UPS activity is often associated with an impairment of IIS, contributing to pathologies such as cancer, diabetes, cardiovascular, and neurodegenerative disorders. Recent findings identified a key role of diverse ubiquitin modifications in insulin signaling decisions, which governs dynamic adaption upon environmental and physiological changes. In this review, we discuss the mutual crosstalk between ubiquitin and insulin signaling pathways in the context of cellular and organismal homeostasis.
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