title: NEDD8 protein is involved in ubiquitinated inclusion bodies.
abstract: Proteolysis by the ubiquitin-proteasome system is considered to play a pathological role in several degenerative diseases that involve ubiquitinated inclusion bodies. In recent years, several ubiquitin-like proteins have been isolated, but it is uncertain whether their roles are associated with protein degradation through the ubiquitin-proteasome system. NEDD8 (neural precursor cell-expressed and developmentally down-regulated gene), which consists of 81 amino acid residues, possesses the highest sequence similarity to ubiquitin. Recent studies have indicated that NEDD8 is covalently ligated to cullin family proteins, which are components of certain ubiquitin E3 ligases, by a pathway analogous to that of ubiquitin. Thus, by focusing on the structural and functional association between NEDD8 and ubiquitin, it would be of interest to know whether the NEDD8 system is involved in pathological disorders of the ubiquitin-proteasome system. This study has examined the immunohistochemical distribution of NEDD8 protein by using a highly purified antibody in normal tissues and in tissues known to contain ubiquitinated inclusions. NEDD8 protein expression was widely observed in most types of tissues. Furthermore, accumulation of the NEDD8 protein was commonly observed in ubiquitinated inclusion bodies, including Lewy bodies in Parkinson's disease, Mallory bodies in alcoholic liver disease, and Rosenthal fibres in astrocytoma. Two of ten cases of neurofibrillary tangles and senile plaques from patients with Alzheimer's disease showed intense staining for NEDD8 as well as for ubiquitin. These findings suggest the possibility that the NEDD8 system is involved in the metabolism of these inclusion bodies via the ubiquitin-proteasome system.
authors.affiliation: First Department of Pathology, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Afroz
authors.initials: A
authors.lastname: Dil Kuazi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kito
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Abe
authors.forename: Ryong-Woon
authors.initials: RW
authors.lastname: Shin
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
authors.forename: Norifumi
authors.initials: N
authors.lastname: Ueda
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000906:Antibodies / Q000032:analysis*; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D016631:Lewy Bodies / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000473:pathology; D000075687:NEDD8 Protein; D016874:Neurofibrillary Tangles / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D014452:Ubiquitins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D011994:Recombinant Proteins; D025801:Ubiquitin; D014452:Ubiquitins