title: CUL4B-deficiency in humans: understanding the clinical consequences of impaired Cullin 4-RING E3 ubiquitin ligase function.
abstract: Cullin's encode the structural components for one of the most abundant E3 ubiquitin ligase families in eukaryotes accounting for as many as 400 distinct E3 ubiquitin ligases. Because of their modular assembly involving combinations of multiple distinct adaptor and substrate receptor proteins, it comes as no surprise that these E3's are implicated in a plethora of fundamental biochemical processes ranging from DNA replication and repair to transcription and development. Herein, we focus on one member of the cullin family, namely the Cullin 4-RING E3 ligases (CRL4's). More specifically, we overview what has been learned about some of the functions of CRL4's from various model systems. We discuss the unexpected association of defective CUL4B with syndromal X-linked mental retardation in humans and speculate on the biochemical consequences and clinical implications of defective CRL4 function. In particular, mutations in CUL4B highlight a previously unappreciated role for CRL4's in neuronal function and cognition in humans.
authors.affiliation: Human DNA Damage Response Disorders Group, Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kerzendorfer
authors.forename: Lesley
authors.initials: L
authors.lastname: Hart
authors.forename: Rita
authors.initials: R
authors.lastname: Colnaghi
authors.forename: Gillian
authors.initials: G
authors.lastname: Carpenter
authors.forename: Diana
authors.initials: D
authors.lastname: Alcantara
authors.forename: Emily
authors.initials: E
authors.lastname: Outwin
authors.forename: Antony M
authors.initials: AM
authors.lastname: Carr
authors.forename: Mark
authors.initials: M
authors.lastname: O'Driscoll
mesh_terms: D003071:Cognition; D044842:Cullin Proteins; D004260:DNA Repair; D004261:DNA Replication; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: C517832:CUL4B protein, human; D044842:Cullin Proteins; D044767:Ubiquitin-Protein Ligases