Degradation for better survival? Role of ubiquitination in epithelial morphogenesis

Abstract

As a prevalent post-translational modification, ubiquitination is essential for many developmental processes. Once covalently attached to the small and conserved polypeptide ubiquitin (Ub), a substrate protein can be directed to perform specific biological functions via its Ub-modified form. Three sequential catalytic reactions contribute to this process, among which E3 ligases serve to identify target substrates and promote the activated Ub to conjugate to substrate proteins. Ubiquitination has great plasticity, with diverse numbers, topologies and modifications of Ub chains conjugated at different substrate residues adding a layer of complexity that facilitates a huge range of cellular functions. Herein, we highlight key advances in the understanding of ubiquitination in epithelial morphogenesis, with an emphasis on the latest insights into its roles in cellular events involved in polarized epithelial tissue, including cell adhesion, asymmetric localization of polarity determinants and cytoskeletal organization. In addition, the physiological roles of ubiquitination are discussed for typical examples of epithelial morphogenesis, such as lung branching, vascular development and synaptic formation and plasticity. Our increased understanding of ubiquitination in epithelial morphogenesis may provide novel insights into the molecular mechanisms underlying epithelial regeneration and maintenance.

Deubiquitinase USP19 modulates apoptotic calcium release and endoplasmic reticulum stress by deubiquitinating BAG6 in triple negative breast cancer

“…Ubiquitination is a reversible process in which deubiquitinases separate ubiquitin molecules from proteins to increase their stability 36–38 . It has been reported to be critical for the regulation of programmed cell death 39,40 .…”

“…Ubiquitination is a reversible process in which deubiquitinases separate ubiquitin molecules from proteins to increase their stability. 36 , 37 , 38 It has been reported to be critical for the regulation of programmed cell death. 39 , 40 A recent publication showed that HOIL1 E3 mediates mono‐ubiquitination of the linear ubiquitin chain assembly complex, resulting in embryonic death upon knockout of HOIL1 in mice.…”

Proteotoxic stress disrupts epithelial integrity by inducing MTOR sequestration and autophagy overactivation

“…RIKE-1 also carries a Cys3HisCys4-type Zinc finger domain at the N-terminus and this group of RING domain proteins includes many E3 ubiquitin ligases [ 63 ]. In fact, E3 ligases are implicated in both proteome balance and epithelial morphogenesis [ 64 ]. Further work is required to elucidate the detailed molecular mechanism of how RIKE-1 controls protein homeostasis by preventing the accumulation of surplus and aberrant protein species.…”

Ehm2 transcript variant 1 inhibits breast cancer progression and increases E-cadherin stability

“…Ubiquitination is the process of ligating an ubiquitin molecule, a 76-amino acid protein that is ubiquitously expressed in all tissues, to a substrate protein, which in turn regulates protein stability and translocation ( 33 ). Importantly, direct and indirect evidence indicates that ubiquitination actively participates in the regulation of core proteins required for epithelial morphogenesis ( 34 , 35 ). Many proteins can be involved in cell motility and invasiveness through regulating ubiquitination of EMT-associated proteins.…”