Sumoylation in Development and Differentiation

Abstract

Tissue morphogenesis is a fascinating aspect of both developmental biology and regeneration of certain adult organs, and timely control of cellular differentiation is a key to these processes. During development, events interrupting cellular differentiation and leading to organ failure are embryonic lethal; likewise, perturbation of differentiation in regenerating tissues leads to dysfunction and disease. At the molecular level, cellular differentiation is orchestrated by a well-coordinated cascade of transcription factors (TFs) and chromatin remodeling complexes that drive gene expression. Altering the localization, stability, or activity of these regulatory elements can affect the sequential organization of the gene expression program and result in failed or abnormal tissue development. An accumulating body of evidence shows that the sumoylation system is a critical modulator of these regulatory cascades. For example, inhibition of the sumoylation system during embryogenesis causes lethality and/or severe abnormalities from invertebrates to mammals. Mechanistically, it is now known that many of the TFs and components of chromatin remodeling complexes that are critical for development and differentiation are targets for SUMO modification, though the specific functional consequences of the modifications remain uncharacterized in many cases. This chapter will address several of the models systems that have been examined for the role of sumoylation in differentiation and development. Understanding the profound regulatory role of SUMO in different tissues should lead not only to a better understanding of developmental biology, stem cell linage control, and the mechanisms of cellular differentiation, but may also lead to the identification of new targets for drug therapy and/or therapeutic manipulation of damaged organs and tissues.

HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network

“…HSF1 is negatively regulated through sumoylation of HSF1 in both C. elegans and mammalian cell culture (Hong et al, 2001;Hietakangas et al, 2003;Anckar et al, 2006;Hietakangas et al, 2006;Das et al, 2017). SUMO protein catalyzes a small ubiquitin like modification, which frequently targets transcription factors to limit activity (Gill 2005;Cubenas-Potts and Matunis 2013;Deyrieux and Wilson 2017;Wotton et al, 2017). Mammals have four genes encoding SUMO, while C. elegans possess a single gene, smo-1 (Kamitani et al, 1998;Jones et al, 2002).…”

Synaptic localization of the SUMOylation‐regulating protease SENP5 in the adult mouse brain

“…The post‐translational modification of proteins through the addition of small ubiquitin‐like modifier (SUMO) proteins regulates a broad range of cellular functions including mitosis, cell differentiation, and synaptic transmission (Deyrieux & Wilson, ; Gwizdek, Casse, & Martin, ; Henley, Craig, & Wilkinson, ; Mukhopadhyay & Dasso, ). SUMOs have thus been implicated in several disease states such as cancer, diabetes, cardiovascular disease, and neurological disorders (Abe et al, ; Eifler & Vertegaal, ; Henley et al, ; Lee, Choi, & Baek, ; Zhang, Chen, Zhou, Yang, & Wang, ).…”

Tissue-specific inhibition of protein sumoylation uncovers diverse SUMO functions during C. elegans vulval development

“…A tissue-specific degradation toolkit to study the SUMO pathway and its targets Posttranslational protein modification via the SUMO pathway is essential for many biological processes (Deyrieux and Wilson 2017). Though, the pleiotropic effects and transient and reversible nature of protein sumoylation has rendered this pathway difficult to study.…”