PARsylation-mediated ubiquitylation: lessons from rare hereditary disease Cherubism

Modification of proteins by ADP-ribose (PARsylation) is catalyzed by the poly(ADP-ribose) polymerase (PARP) family of enzymes exemplified by PARP1, which controls chromatin organization and DNA repair. Additionally, PARsylation induces ubiquitylation and proteasomal degradation of its substrates because PARsylation creates a recognition site for E3-ubiquitin ligase. The steady-state levels of the adaptor protein SH3-domain binding protein 2 (3BP2) is negatively regulated by tankyrase (PARP5), which coordinates ubiquitylation of 3BP2 by the E3-ligase ring finger protein 146 (RNF146). 3BP2 missense mutations uncouple 3BP2 from tankyrase-mediated negative regulation and cause Cherubism, an autosomal dominant autoinflammatory disorder associated with craniofacial dysmorphia. In this review, we summarize the diverse biological processes, including bone dynamics, metabolism, and Toll-like receptor (TLR) signaling controlled by tankyrase-mediated PARsylation of 3BP2, and highlight the therapeutic potential of this pathway

<Original Paper>Effects of Intervention on Seating for Elderly Wheelchair Users

The purpose of this paper is to report the results of intervention on the fit of seating for elderly wheelchair users who use foot propulsion. The elderly users, who lived in care facilities, were provided with improved wheelchairs for about two months while we investigated the seating posture, independent mobility, and degree of satisfaction during use. The results of the investigation are as follows: (1) Seating pressure for the subjects who used the fitted wheelchair tended to decrease. (2) Independent mobility for the subjects using the fitted wheelchair tended to decrease. On the other hand, cases where the independent mobility improved were also observed. (3) Subjects were satisfied with the comfortable seating of the improved wheelchair. However, the small-sized elderly subjects were dissatisfied with the transfer, the meal action, and the fitted seat