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Full-Text Articles in Life Sciences
Regulation Of Atg4b Stability By Rnf5 Limits Basal Levels Of Autophagy And Influences Susceptibility To Bacterial Infection, E. Kuang, Cheryl Okumura, S. Sheffy-Levin, T. Varsano, V. Shu, J. Qi, I. Niesman, H. Yang, C. LóPez-OtíN, W. Yang, J. Reed, L. Broday, V. Nizet, Z. Ronai
Regulation Of Atg4b Stability By Rnf5 Limits Basal Levels Of Autophagy And Influences Susceptibility To Bacterial Infection, E. Kuang, Cheryl Okumura, S. Sheffy-Levin, T. Varsano, V. Shu, J. Qi, I. Niesman, H. Yang, C. LóPez-OtíN, W. Yang, J. Reed, L. Broday, V. Nizet, Z. Ronai
Cheryl Okumura
Autophagy is the mechanism by which cytoplasmic components and organelles are degraded by the lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, and multiple forms of cellular stress. Here, we show that the membrane-associated E3 ligase RNF5 regulates basal levels of autophagy by controlling the stability of a select pool of the cysteine protease ATG4B. RNF5 controls the membranal fraction of ATG4B and limits LC3 (ATG8) processing, which is required for phagophore and autophagosome formation. The association of ATG4B with—and regulation of its ubiquitination and stability by—RNF5 is seen primarily under normal growth conditions. Processing of …
A New Pharmacological Agent (Akb-4924) Stabilizes Hypoxia Inducible Factor (Hif) And Increases Skin Innate Defenses Against Bacterial Infection., Cheryl Okumura, A. Hollands, D. Tran, J. Olson, S. Dahesh, M. Von KöCkritz-Blickwede, W. Thienphrapa, C. Corle, S. Jeung, A. Kotsakis, R. Shalwitz, R. Johnson, V. Nizet
A New Pharmacological Agent (Akb-4924) Stabilizes Hypoxia Inducible Factor (Hif) And Increases Skin Innate Defenses Against Bacterial Infection., Cheryl Okumura, A. Hollands, D. Tran, J. Olson, S. Dahesh, M. Von KöCkritz-Blickwede, W. Thienphrapa, C. Corle, S. Jeung, A. Kotsakis, R. Shalwitz, R. Johnson, V. Nizet
Cheryl Okumura
Hypoxia inducible factor-1 (HIF-1) is a transcription factor that is a major regulator of energy homeostasis and cellular adaptation to low oxygen stress. HIF-1 is also activated in response to bacterial pathogens and supports the innate immune response of both phagocytes and keratinocytes. In this work, we show that a new pharmacological compound AKB-4924 (Akebia Therapeutics) increases HIF-1α levels and enhances the antibacterial activity of phagocytes and keratinocytes against both methicillin-sensitive and -resistant strains of Staphylococcus aureus in vitro. AKB-4924 is also effective in stimulating the killing capacity of keratinocytes against the important opportunistic skin pathogens Pseudomonas aeruginosa and Acinitobacter …
Novel Role Of The Transcription Factor Hif-1Α In The Formation Of Mast Cell Extracellular Traps., K. Branitzki-Heinemann, Cheryl Okumura, L. VöLlger, Y. Kawakami, T. Kawakami, H. Naim, V. Nizet, M. Von KöCkritz-Blickwede
Novel Role Of The Transcription Factor Hif-1Α In The Formation Of Mast Cell Extracellular Traps., K. Branitzki-Heinemann, Cheryl Okumura, L. VöLlger, Y. Kawakami, T. Kawakami, H. Naim, V. Nizet, M. Von KöCkritz-Blickwede
Cheryl Okumura
MCs (mast cells) are critical components of the host innate immune defence against bacterial pathogens, providing a variety of intra- and extra-cellular antimicrobial functions. In the present study we show, for the first time, that the transcriptional regulator HIF-1α (hypoxia-inducible factor-1α) mediates the extracellular antimicrobial activity of human and murine MCs by increasing the formation of MCETs (MC extracellular traps).
Pharmacological Inhibition Of The Clpxp Protease Increases Bacterial Susceptibility To Host Cathelicidin Antimicrobial Peptides And Cell-Envelope Active Antibiotics., S. Mcgillivray, D. Tran, N. Ramadoss, J. Alumasa, Cheryl Okumura, G. Sakoulas, M. Vaughn, D. Zhang, K. Keiler, V. Nizet
Pharmacological Inhibition Of The Clpxp Protease Increases Bacterial Susceptibility To Host Cathelicidin Antimicrobial Peptides And Cell-Envelope Active Antibiotics., S. Mcgillivray, D. Tran, N. Ramadoss, J. Alumasa, Cheryl Okumura, G. Sakoulas, M. Vaughn, D. Zhang, K. Keiler, V. Nizet
Cheryl Okumura
The ClpXP protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. Here we identified a pharmacological inhibitor of the ClpXP protease, F2, and evaluated its action in Bacillus anthracis and Staphylococcus aureus. We found that F2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane such as penicillin and daptomycin in B. anthracis and drug resistant strains of S. aureus. ClpXP inhibition represents a novel therapeutic strategy to simultaneously sensitize pathogenic bacteria to host defenses and pharmaceutical antibiotics.