DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy

Abstract

Abstract. DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease. DJ-1 has a proteaselike structure and transthyretin (TTR), a protein causing familial amyloidotic polyneuropathy (FAP), was identified as a substrate for DJ-1 protease in this study. Both TTR and DJ-1 were secreted into the culture medium under normal conditions, and secreted TTR was not aggregated. Under oxidative conditions, TTR but not DJ-1 was secreted into the culture medium, resulting in aggregation. Mirror images of both the expression patterns and solubility of DJ-1 and TTR were observed in tissues of FAP patients, and an unoxidized form of DJ-1, an inactive form, was secreted into the serum of FAP patients. These results suggest that oxidative stress to cells abrogates secretion of DJ-1 and that secreted DJ-1 degrades aggregated TTR to protect against the onset of FAP.

Numerical Simulation on a Horizontal Flow Pattern of Jet-induced Rotary Sloshing in a Cylindrical Container

“…Outside the rotary sloshing, at zϭ5.0, 8.0 and 12 (cm), the airflow seems to be almost circular of which the centre is around the surface swell. It may be seen that this airflow pattern outside the sloshing is similar to the two-liquid layer case of Yoshida et al 10) (see Fig. 4 of their paper).…”

Epidermal Growth Factor-dependent Activation of the Extracellular Signal-regulated Kinase Pathway by DJ-1 Protein through Its Direct Binding to c-Raf Protein

“…6), indicating that DJ-1 is able to activate c-Raf without other factors under these conditions. Although DJ-1 has several enzymatic activities, including protease (37)(38)(39)(40) and glyoxalase activities (41)(42)(43)(44), there is no report showing that DJ-1 is a protein kinase and that DJ-1 has a structural motif for kinase (3)(4)(5). These results therefore suggest that DJ-1 enhances self-phosphorylation activity of c-Raf without a role as kinase.…”

The Role of Cysteine Oxidation in DJ-1 Function and Dysfunction

“…The diversity of disease states in which DJ-1 is implicated reflects the current view that it is a multifunctional protein with several proposed biochemical and cellular activities. Among these proposed roles for DJ-1 are a redox-regulated chaperone (48,80), an RNA binding protein (11,92), a cysteine protease (16,42,70), a transcriptional coactivator (18,104,108,109), and a protein that interacts with the apoptosis-implicated proteins Daxx (38), apoptosis signal regulating kinase 1 (ASK1) (36,63,95), and p53 (14,25,26,40,83). In addition, DJ-1 also binds to proteins related to androgen receptor function (81,87,91) and sumoylation (25,82), although the functional role of these interactions requires clarification.…”