The ESX-1 secretion system plays a critical role in the virulence of Mycobacterium tuberculosis and M. marinum. To date, three proteins are known to be secreted by ESX-1 and necessary for virulence, two of which are CFP-10 and ESAT-6. The ESX-1 secretion and the virulence mechanisms are not well understood. In this study, we have examined the M. marinum secretomes and identified four proteins specific to ESX-1. Two of those are CFP-10 and ESAT-6, and the other two are novel: MM1553 (homologous to Rv3483c) and Mh3881c (homologous to Rv3881c). We have shown that Mh3881c, CFP-10 and ESAT-6 are co-dependent for secretion. Mh3881c is being cleaved at close to the C-terminus during secretion, and the C-terminal portion is critical to the co-dependent secretion, the ESAT-6 cellular levels, and interaction with ESAT-6. The co-dependent secretion is required for M. marinum intracellular growth in macrophages, where the Mh3881c C-terminal portion plays a critical role. The role of the co-dependent secretion in intracellular growth correlates with its role in inhibiting phagosome maturation. Both the secretion and the virulence defects of the Mh3881c mutant are complemented by Mh3881c or its M. tuberculosis homologue Rv3881c, suggesting that in M. tuberculosis, Rv3881c has similar functions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1365-2958.2007.05959.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PTPN23-dependent ESCRT machinery functions as a cell death checkpoint.
Nat Commun
November 2024
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Cell death plasticity is crucial for modulating tissue homeostasis and immune responses, but our understanding of the molecular components that regulate cell death pathways to determine cell fate remains limited. Here, a CRISPR screen of acute myeloid leukemia cells identifies protein tyrosine phosphatase non-receptor type 23 (PTPN23) as essential for survival. Loss of PTPN23 activates nuclear factor-kappa B, apoptotic, necroptotic, and pyroptotic pathways by causing the accumulation of death receptors and toll-like receptors (TLRs) in endosomes.
View Article and Find Full Text PDFComprehensive functional evaluation of head and neck squamous cell carcinoma with BH3-profiling demonstrates apoptotic competency and therapeutic efficacy of BH3-mimetics.
Oral Oncol
December 2024
Department of Pathology, Montefiore Medical Center / Albert Einstein College of Medicine, Bronx, NY, USA; Department of Otorhinolaryngology - Head and Neck Surgery, Montefiore Medical Center / Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address:
Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC's highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood.
View Article and Find Full Text PDFHypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.
Front Cell Dev Biol
August 2024
Department of Biology, University of York, York, United Kingdom.
The events that control breast cancer progression and metastasis are complex and intertwined. Hypoxia plays a key role both in oncogenic transformation and in fueling the metastatic potential of breast cancer cells. Here we review the impact of hypoxia on epigenetic regulation of breast cancer, by interfering with multiple aspects of the tumour microenvironment.
View Article and Find Full Text PDFNon-arterial line cardiac output calculation misclassifies exercise pulmonary hypertension and increases risk of data loss particularly in black, scleroderma and Raynaud's patients during invasive exercise testing.
Eur Respir J
July 2024
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA, USA
Article Synopsis
- - The direct Fick principle is used to calculate cardiac output (CO) to identify conditions like exercise pulmonary hypertension (ePH) by comparing arterial and mixed venous values, which can lead to inconsistencies based on the presence of an arterial catheter.
- - A study analyzed 296 invasive cardiopulmonary exercise tests, revealing significant discrepancies in oxygen saturation and CO calculations between arterial and non-arterial methods, which resulted in a higher rate of data loss and misclassification of pre- and post-capillary ePH.
- - The findings suggest that relying on non-arterial measures during exercise testing can misclassify ePH, particularly affecting patients with conditions like scleroderma, Raynaud's, and black individuals
PROTAC-Mediated Dual Degradation of BCL-xL and BCL-2 Is a Highly Effective Therapeutic Strategy in Small-Cell Lung Cancer.
Cells
March 2024
Department of Biochemistry & Structural Biology, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!