Deubiquitinase catalytic activity of MYSM1 is essential in vivo for hematopoiesis and immune cell development.

Myb-like SWIRM and MPN domains 1 (MYSM1) is a chromatin binding protein with deubiquitinase (DUB) catalytic activity. Rare MYSM1 mutations in human patients result in an inherited bone marrow failure syndrome, highlighting the biomedical significance of MYSM1 in the hematopoietic system. We and others characterized Mysm1-knockout mice as a model of this disorder and established that MYSM1 regulates hematopoietic function and leukocyte development in such models through different mechanisms.

USP15: a review of its implication in immune and inflammatory processes and tumor progression.

The covalent post-translational modification of proteins by ubiquitination not only influences protein stability and half-life, but also several aspects of protein function including enzymatic activity, sub-cellular localization, and interactions with binding partners. Protein ubiquitination status is determined by the action of large families of ubiquitin ligases and deubiquitinases, whose combined activities regulate many physiological and cellular pathways. The Ubiquitin Specific Protease (USP) family is one of 8 subfamilies of deubiquitinating enzymes composed of more than 50 members.

ZBTB7B (ThPOK) Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis.

We used a genome-wide screen in -ethyl--nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the ZBTB7B (ThPOK) protein in which homozygosity causes protection against experimental cerebral malaria (ECM) caused by infection with ANKA. homozygous mice show a defect in the lymphoid compartment expressed as severe reduction in the number of single-positive CD4 T cells in the thymus and in the periphery, reduced brain infiltration of proinflammatory leukocytes in ANKA-infected mice, and reduced production of proinflammatory cytokines by primary T cells and Dampening of proinflammatory immune responses in mice is concomitant to increased susceptibility to infection with avirulent ( BCG) and virulent ( H37Rv) mycobacteria.

Author Correction: Identification and Characterization of USP7 Targets in Cancer Cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

USP7 Regulates Cytokinesis through FBXO38 and KIF20B.

The ubiquitin specific protease 7 (USP7 or HAUSP) is known to regulate a variety of cellular processes by binding and deubiquitylating specific target proteins. To gain a more comprehensive understanding of its interactions and functions, we used affinity purification coupled to mass spectrometry to profile USP7 interactions. This revealed a novel interaction with FBXO38, a poorly characterized F-box protein.

Identification and Characterization of USP7 Targets in Cancer Cells.

The ubiquitin specific protease, USP7, regulates multiple cellular pathways relevant for cancer through its ability to bind and sometimes stabilize specific target proteins through deubiquitylation. To gain a more complete profile of USP7 interactions in cancer cells, we performed affinity purification coupled to mass spectrometry to identify USP7 binding targets in gastric carcinoma cells. This confirmed reported associations of USP7 with USP11, PPM1G phosphatase and TRIP12 E3 ubiquitin ligase as well as identifying novel interactions with two DEAD/DEAH-box RNA helicases, DDX24 and DHX40.

Affinity Purification-Mass Spectroscopy Methods for Identifying Epstein-Barr Virus-Host Interactions.

Considerable insight into the function and mechanism of action of viral proteins has come from identifying the cellular proteins with which they interact. In recent years, mass spectrometry-based methods have emerged as the method of choice for protein interaction discovery due to their comprehensive and unbiased nature. Methods involving single affinity purifications of epitope-tagged viral proteins (AP-MS) and tandem affinity purifications of viral proteins with two purification tags (TAP tagging) have both been used to identify novel host interactions with EBV proteins.

Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7.

Herpes simplex virus-1 immediate-early protein ICP0 activates viral genes during early stages of infection, affects cellular levels of multiple host proteins and is crucial for effective lytic infection. Being a RING-type E3 ligase prone to auto-ubiquitination, ICP0 relies on human deubiquitinating enzyme USP7 for protection against 26S proteasomal mediated degradation. USP7 is involved in apoptosis, epigenetics, cell proliferation and is targeted by several herpesviruses.

Proteomics methods for discovering viral-host interactions.

The functions of many viral proteins involve direct interactions with specific host proteins. Therefore considerable insight into the functions of a viral protein and its mechanisms of action can come from applying proteomics approaches to viral proteins in order to identify their cellular binding partners. In this chapter we describe proteomics approaches that have proven to be the most useful in identifying host interactions of viral proteins in human cells.

Metaproteomic analysis of a winter to spring succession in coastal northwest Atlantic Ocean microbial plankton.

In this study, we used comparative metaproteomics to investigate the metabolic activity of microbial plankton inhabiting a seasonally hypoxic basin in the Northwest Atlantic Ocean (Bedford Basin). From winter to spring, we observed a seasonal increase in high-affinity membrane transport proteins involved in scavenging of organic substrates; Rhodobacterales transporters were strongly associated with the spring phytoplankton bloom, whereas SAR11 transporters were abundant in the underlying waters. A diverse array of transporters for organic compounds were similar to the SAR324 clade, revealing an active heterotrophic lifestyle in coastal waters.