title: The role of ubiquitin-binding domains in human pathophysiology.
abstract: Ubiquitination, a fundamental post-translational modification (PTM) resulting in the covalent attachment of ubiquitin (Ub) to a target protein, is currently implicated in several key cellular processes. Although ubiquitination was initially associated with protein degradation, it is becoming increasingly evident that proteins labeled with polyUb chains of specific topology and length are activated in an ever-expanding repertoire of specific cellular processes. In addition to their involvement in the classical protein degradation pathways they are involved in DNA repair, kinase regulation and nuclear factor-κB (NF-κB) signaling. The sorting and processing of distinct Ub signals is mediated by small protein motifs, known as Ub-binding domains (UBDs), which are found in proteins that execute disparate biological functions. The involvement of UBDs in several biological pathways has been revealed by several studies which have highlighted the vital role of UBDs in cellular homeostasis. Importantly, functional impairment of UBDs in key regulatory pathways has been related to the development of pathophysiological conditions, including immune disorders and cancer. In this review, we present an up-to-date account of the crucial role of UBDs and their functions, with a special emphasis on their functional impairment in key biological pathways and the pathogenesis of several human diseases. The still under-investigated topic of Ub-UBD interactions as a target for developing novel therapeutic strategies against many diseases is also discussed.
authors.affiliation: The Cyprus Institute of Neurology and Genetics , Nicosia , Cyprus .
authors.forename: Kleitos
authors.initials: K
authors.lastname: Sokratous
authors.forename: Andreas
authors.initials: A
authors.lastname: Hadjisavvas
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Kyriacos
authors.initials: K
authors.lastname: Kyriacou
mesh_terms: D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000378:metabolism / Q000503:physiopathology; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D025801:Ubiquitin
keywords: UBD; Ubiquitin; immunodeficiency disorders; signaling pathways; tumorigenesis; ubiquitination