Biomedical subjects

A E Elia

Publications and source records attributed to A E Elia.

4 recordsLinked to original sources

PubMed2006

Onset and progression of primary torsion dystonia in sporadic and familial cases.

Four hundred and sixty records of patients with primary torsion dystonia (296 women and 164 men) were evaluated. The mean age at disease onset was 48.3 +/- 17.7 years; 13 patients carried the DYT1 CAG deletion. The distribution of age at onset was represented by a bi-modal curve, with a nadir at 21 year separating early onset from late onset cases. In 15.9% of cases there was a positive family history of dystonia. Cranial, cervical or lower limb onset was more common amongst women (M:F ratios were 1:2.7, 1:1.9, and 1:3); by contrast, onset in the upper limb was more common in men (M:F ratio 2.2:1). As expected, disease progression was more pronounced in cases with early onset; it was reckoned that onset at or above 32 years was associated with a negligible likelihood to progress to a generalized form. The mean age at onset of familial cases was 44.8 +/- 11.2 years, significantly lower than the mean age at onset of sporadic cases (53.5 +/- 13.4 years). Familial cases were characterized by more sites involved throughout disease course. Familial cases had a higher tendency to progress to a segmental or generalized form than sporadic cases.

Adolescent↗

PubMed2005

The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease.

Mutations in the PINK1 gene cause autosomal recessive parkinsonism characterized by early onset and a variable phenotypic presentation. A patient homozygous for the Ala168Pro mutation has been fully characterized clinically. Apart from onset at age 39 years and the excellent and sustained response to levodopa, all clinical and laboratory features, including SPECT and assessment of autonomic function, were indistinguishable from typical idiopathic Parkinson disease.

Age of Onset↗

PubMed2001

Phosphoserine/threonine-binding domains.

Phosphorylation of proteins on serine and threonine residues has traditionally been viewed as a means to allosterically regulate catalytic activity. Research within the past five years, however, has revealed that serine/threonine phosphorylation can also directly result in the formation of multimolecular signaling complexes through specific interactions between phosphoserine/threonine (pSer/Thr)-binding modules and phosphorylated sequence motifs. pSer/Thr-binding proteins and domains currently include 14-3-3, WW domains, forkhead-associated domains, and, tentatively, WD40 repeats and leucine-rich regions. It seems likely that additional modules will be found in the future. The amino acid sequences recognized by these pSer/Thr-binding modules show partial overlap with the optimal phosphorylation motifs for different protein kinase subfamilies, allowing the formation of specific signaling complexes to be controlled through combinatorial interactions between particular upstream kinases and a particular binding module. The structural basis for pSer/Thr binding differs dramatically between 14-3-3 proteins, WW domains and forkhead-associated domains, suggesting that their pSer/Thr binding function was acquired through convergent evolution.

Animals↗

PubMed2000

A novel ability of Smad3 to regulate proteasomal degradation of a Cas family member HEF1.

Smad3 is a key signal transducer of transforming growth factor-ss (TGF-ss) and activin, and is known to be a DNA-binding transcriptional regulator. Here we report a novel property of Smad3 in regulating the proteasomal degradation of the human enhancer of filamentation 1 (HEF1), which is a member of the Cas family of cytoplasmic docking proteins. Our studies revealed that Smad3 interacts with HEF1 and triggers the proteasomal degradation of HEF1 in overexpression systems. In addition, TGF-ss stimulation induces rapid proteasomal degradation of endogenous HEF1 in different TGF-ss-responsive cell lines. Interestingly, the degradation of HEF1 protein in epithelial cells is followed closely by an increase in HEF1 mRNA, resulting in a time-dependent increase in HEF1 protein level in TGF-ss-treated cells. Furthermore, we observed that an elevated HEF1 protein level inhibits TGF-ss-induced Smad3-mediated gene responses. These data provide the first evidence for a novel cytoplasmic activity of Smad3 in regulating proteasomal degradation of HEF1 and also suggest a role for HEF1 in a negative feedback mechanism of the TGF-ss signaling pathway.

Adaptor Proteins, Signal Transducing↗