Parkin Alternative Splicing: Not only Parkinsonism
نویسندگان
چکیده
The alternative splicing (AS) mechanism is considered the major driving force of transcriptome and proteome diversity. Itrelies on a delicate and finely tuned interplay among a great number of molecular elements. The crucial action of AS in the regulation of diverse biological processes is not limited to physiological states, but is mirrored in the growing list of human diseases associated with known or suspected splicing defects, including neurodegenerative and oncologicaldiseases. In these pathologies, the AS regulation of PARK2gene (also called parkin RBR E3 ubiquitin protein ligase), one of the largest in our genome, seems to play a fundamental role. Here, we will briefly review some major data concerning the genetic organization, the transcription regulation, the structure of the protein and the relative molecular functions of PARK2. Then we will focuson the current knowledge about PARK2 alternative spliced isoforms and their implication in human diseases.
منابع مشابه
parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism
BACKGROUND parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of whi...
متن کاملAlternative Splicing Generates Different Parkin Protein Isoforms: Evidences in Human, Rat, and Mouse Brain
Parkinson protein 2, E3 ubiquitin protein ligase (PARK2) gene mutations are the most frequent causes of autosomal recessive early onset Parkinson's disease and juvenile Parkinson disease. Parkin deficiency has also been linked to other human pathologies, for example, sporadic Parkinson disease, Alzheimer disease, autism, and cancer. PARK2 primary transcript undergoes an extensive alternative sp...
متن کاملAdaptive alternative splicing correlates with less environmental risk of parkinsonism.
BACKGROUND/OBJECTIVE Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain's capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. METHODS Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetr...
متن کاملA molecular explanation for the recessive nature of parkin-linked Parkinson’s disease
Mutations in the park2 gene, encoding the RING-inBetweenRING-RING E3 ubiquitin ligase parkin, cause 50% of autosomal recessive juvenile Parkinsonism cases. More than 70 known pathogenic mutations occur throughout parkin, many of which cluster in the inhibitory amino-terminal ubiquitin-like domain, and the carboxy-terminal RING2 domain that is indispensable for ubiquitin transfer. A structural r...
متن کاملParkin mutations are frequent in patients with isolated early-onset parkinsonism.
Parkin gene mutations are reported to be a major cause of early-onset parkinsonism (age at onset < or = 45 years) in families with autosomal recessive inheritance and in isolated juvenile-onset parkinsonism (age at onset <20 years). However, the precise frequency of parkin mutations in isolated cases is not known. In order to evaluate the frequency of parkin mutations in patients with isolated ...
متن کامل