Inhibition of proteasomal degradation by the Gly-Ala repeat of Epstein–Barr virus is influenced by the length of the repeat and the strength of the degradation signal

The Gly-Ala repeat (GAr) of the Epstein–Barr virus nuclear antigen-1 is a transferable element that inhibits in cis ubiquitin/proteasome-dependent proteolysis. We have investigated this inhibitory activity by using green fluorescent protein-based reporters that have been targeted for proteolysis by N end rule or ubiquitin-fusion degradation signals, resulting in various degrees of destabilization. Degradation of the green fluorescent protein substrates was inhibited on insertion of a 25-aa GAr, but strongly destabilized reporters were protected only partially. Protection could be enhanced by increasing the length of the repeat. However, reporters containing the Ub-R and ubiquitin-fusion degradation signals were degraded even in the presence of a 239-aa GAr. In accordance, insertion of a powerful degradation signal relieved the blockade of proteasomal degradation in Epstein–Barr virus nuclear antigen-1. Our findings suggest that the turnover of natural substrates may be finely tuned by GAr-like sequences that counteract targeting signals for proteasomal destruction.

The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the protein huntingtin (htt). Pathogenesis in HD appears to involve the formation of ubiquitinated neuronal intranuclear inclusions containing N-terminal mutated htt, abnormal protein interactions, and the aggregate sequestration of a variety of proteins (noticeably, transcription factors). To identify novel htt-interacting proteins in a simple model system, we used a yeast two-hybrid screen with a Caenorhabditis elegans activation domain library. We found a predicted WW domain protein (ZK1127.9) that interacts with N-terminal fragments of htt in two-hybrid tests. A human homologue of ZK1127.9 is CA150, a transcriptional coactivator with a N-terminal insertion that contains an imperfect (Gln-Ala)38 tract encoded by a polymorphic repeat DNA. CA150 interacted in vitro with full-length htt from lymphoblastoid cells. The expression of CA150, measured immunohistochemically, was markedly increased in human HD brain tissue compared with normal age-matched human brain tissue, and CA150 showed aggregate formation with partial colocalization to ubiquitin-positive aggregates. In 432 HD patients, the CA150 repeat length explains a small, but statistically significant, amount of the variability in the onset age. Our data suggest that abnormal expression of CA150, mediated by interaction with polyglutamine-expanded htt, may alter transcription and have a role in HD pathogenesis.

Library and Information Science Education and eScience: The Current State of ALA Accredited MLS/MLIS Programs in preparing Librarians and Information Professionals for eScience Needs

The purpose of this study is multifaceted: 1) to describe eScience research in acomprehensive way; 2) to help library and information specialists understand the realm of eScience research and the information needs of the community and demonstrate the importance of LIS professionals within the eScience domain; 3) and to explore the current state of curricular content of ALA accredited MLS/MLIS programs to understand the extent to which they prepare new professionals within eScience librarianship. The literature review focuses heavily on eScientists and other data-driven researchers’ information service needs in addition to demonstrating how and why librarians and information specialists can and should fulfill these service gaps and information needs within eScience research. By looking at the current curriculum of American Library Association (ALA) accredited MLS/MLIS programs, we can identify potential gaps in knowledge and where to improve in order to prepare and train new MLS/MLIS graduates to fulfill the needs of eScientists. This investigation is meant to be informative and can be used as a tool for LIS programs to assess their curriculums in comparison to the needs of eScience and other data-driven and networked research. Finally, this investigation will provide awareness and insight into the services needed to support a thriving eScience and data-driven research community to the LIS profession.