Correction: Correction: Regulation of Neuronal Morphogenesis and Positioning by Ubiquitin-Specific Proteases in the Cerebellum.
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ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4526667 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Correction: Correction: Regulation of Neuronal Morphogenesis and Positioning by Ubiquitin-Specific Proteases in the Cerebellum.
PloS one 20150805 8
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Project description:Staphylococcus aureus is a Gram-positive opportunistic pathogen that has colonized nearly 30% of the human population and can cause life-threatening infections. S. aureus exports a variety of virulence factors, such as a novel set of extracellular serine protease-like proteins (Spls). Spls are expressed by most clinical isolates of S. aureus, but their pathophysiological substrates and role during the infection are largely unknown. Here we characterized the substrate and cleavage specificity of recombinantly expressed SplA and SplB proteins. We identified a group of ubiquitin or ubiquitin-like modifying enzymes including deubiquitinating enzymes from human as well as from bacterial sources to be so far unknown SplA and SplB substrates. Distinct cleavage sites within these substrates for SplA (YLY↓T, FMY↓N) and SplB (VCD↓S) were identified by mass spectrometry and confirmed by site-directed mutagenesis of the target proteins. Since many cellular immune signaling pathways are tightly regulated by ubiquitination, the specific cleavage of ubiquitin modifying enzymes strongly suggests a specific role of Spls in manipulating immune signaling and in competing with other bacteria.
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Project description:Ubiquitin-specific proteases (USPs) emerge as key regulators of numerous cellular processes and account for the bulk of human deubiquitinating enzymes (DUBs). Their modular structure, mostly annotated by sequence homology, is believed to determine substrate recognition and subcellular localization. Currently, a large proportion of known human USP sequences are not annotated either structurally or functionally, including regions both within and flanking their catalytic cores. To extend the current understanding of human USPs, we applied consensus fold recognition to the unannotated content of the human USP family. The most interesting discovery was the marked presence of reliably predicted ubiquitin-like (UBL) domains in this family of enzymes. The UBL domain thus appears to be the most frequently occurring domain in the human USP family, after the characteristic catalytic domain. The presence of multiple UBL domains per USP protein, as well as of UBL domains embedded in the USP catalytic core, add to the structural complexity currently recognized for many DUBs. Possible functional roles of the newly uncovered UBL domains of human USPs, including proteasome binding, and substrate and protein target specificities, are discussed.
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Project description:Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.
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Project description:affy_ath_2012_05 - affy_ath_2012_05 - The main objective is to determinate the influence of Ubiquitin-Like Proteases in plant transcriptional modulation. The experiment will also allow us to find what transcriptional cues are particularly affected in the mutants relatively to wild-type.-Seeds were stratified for 3 days at 4ºC in the dark. Afterwards, seeds were surface sterilized, sown onto MS media and grown at 23ºC, with 100 µE light condition, in long days (16h L/8h D). Each MS plate was dived in four, corresponding to a genotype (Col, AB, SIZ1 or SAB), and 10 seeds were sown per genotype. After 10 days, seedlings were collected and frozen in liquid nitrogen. Each replicate was made of ~40 seedlings coming from 4 different MS plates. Frozen plant material was grounded in an eppendorf tube using a mini pestle. RNA was extracted using RNeasy Plant Mini kit (QIAGEN cat.74904), following the manufacturer instructions (QIAGEN, Hilden, Germany). The RNA samples were DNase treated (Recombinant DNase I, Takara Biotechnology, Dalian, China) and subsequently cleaned by column using RNeasy Plant Mini kit (QIAGEN, Hilden, Germany). 12 arrays - ATH1; gene knock out Col [wild type] AB [knock out / insertional mutagen /T-Dna] SIZ1 [knock out / insertional mutagen /T-Dna] SAB [knock out / insertional mutagen /T-Dna] . More information about this study can be found at : http://urgv.evry.inra.fr/cgi-bin/projects/CATdb/consult_project.pl?project_id=326
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