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  1. Article ; Online: A Versatile Transcription Factor Biosensor System Responsive to Multiple Aromatic and Indole Inducers.

    Nasr, Mohamed A / Timmins, Logan R / Martin, Vincent J J / Kwan, David H

    ACS synthetic biology

    2022  Volume 11, Issue 4, Page(s) 1692–1698

    Abstract: Allosteric transcription factor (aTF) biosensors are valuable tools for engineering microbes toward a multitude of applications in metabolic engineering, biotechnology, and synthetic biology. One of the challenges toward constructing functional and ... ...

    Abstract Allosteric transcription factor (aTF) biosensors are valuable tools for engineering microbes toward a multitude of applications in metabolic engineering, biotechnology, and synthetic biology. One of the challenges toward constructing functional and diverse biosensors in engineered microbes is the limited toolbox of identified and characterized aTFs. To overcome this, extensive bioprospecting of aTFs from sequencing databases, as well as aTF ligand-specificity engineering are essential in order to realize their full potential as biosensors for novel applications. In this work, using the TetR-family repressor CmeR from
    MeSH term(s) Biosensing Techniques ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Indoles ; Ligands ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Salicylates/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Indoles ; Ligands ; Salicylates ; Transcription Factors ; indole (8724FJW4M5)
    Language English
    Publishing date 2022-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2161-5063
    ISSN (online) 2161-5063
    DOI 10.1021/acssynbio.2c00063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Caveolin-1 promotes mitochondrial health and limits mitochondrial ROS through ROCK/AMPK regulation of basal mitophagic flux.

    Timmins, Logan R / Ortiz-Silva, Milene / Joshi, Bharat / Li, Y Lydia / Dickson, Fiona H / Wong, Timothy H / Vandevoorde, Kurt R / Nabi, Ivan R

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2023  Volume 38, Issue 1, Page(s) e23343

    Abstract: Caveolin-1 (CAV1), the main structural component of caveolae, is phosphorylated at tyrosine-14 (pCAV1), regulates signal transduction, mechanotransduction, and mitochondrial function, and plays contrasting roles in cancer progression. We report that ... ...

    Abstract Caveolin-1 (CAV1), the main structural component of caveolae, is phosphorylated at tyrosine-14 (pCAV1), regulates signal transduction, mechanotransduction, and mitochondrial function, and plays contrasting roles in cancer progression. We report that CRISPR/Cas9 knockout (KO) of CAV1 increases mitochondrial oxidative phosphorylation, increases mitochondrial potential, and reduces ROS in MDA-MB-231 triple-negative breast cancer cells. Supporting a role for pCAV1, these effects are reversed upon expression of CAV1 phosphomimetic CAV1 Y14D but not non-phosphorylatable CAV1 Y14F. pCAV1 is a known effector of Rho-associated kinase (ROCK) signaling and ROCK1/2 signaling mediates CAV1 promotion of increased mitochondrial potential and decreased ROS production in MDA-MB-231 cells. CAV1/ROCK control of mitochondrial potential and ROS is caveolae-independent as similar results were observed in PC3 prostate cancer cells lacking caveolae. Increased mitochondrial health and reduced ROS in CAV1 KO MDA-MB-231 cells were reversed by knockdown of the autophagy protein ATG5, mitophagy regulator PINK1 or the mitochondrial fission protein Drp1 and therefore due to mitophagy. Use of the mitoKeima mitophagy probe confirmed that CAV1 signaling through ROCK inhibited basal mitophagic flux. Activation of AMPK, a major mitochondrial homeostasis protein inhibited by ROCK, is inhibited by CAV1-ROCK signaling and mediates the increased mitochondrial potential, decreased ROS, and decreased basal mitophagy flux observed in wild-type MDA-MB-231 cells. CAV1 regulation of mitochondrial health and ROS in cancer cells therefore occurs via ROCK-dependent inhibition of AMPK. This study therefore links pCAV1 signaling activity at the plasma membrane with its regulation of mitochondrial activity and cancer cell metabolism through control of mitophagy.
    MeSH term(s) Male ; Humans ; Caveolin 1/genetics ; Caveolin 1/metabolism ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Reactive Oxygen Species/metabolism ; Mechanotransduction, Cellular ; Mitochondria/metabolism ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Mitochondrial Proteins/metabolism ; rho-Associated Kinases/genetics ; rho-Associated Kinases/metabolism
    Chemical Substances Caveolin 1 ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; Reactive Oxygen Species ; Mitochondrial Proteins ; ROCK1 protein, human (EC 2.7.11.1) ; rho-Associated Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2023-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202201872RR
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2266: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 296: Show issues

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  3. Article ; Online: Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression.

    Wong, Timothy H / Dickson, Fiona H / Timmins, Logan R / Nabi, Ivan R

    Cancer metastasis reviews

    2020  Volume 39, Issue 2, Page(s) 455–469

    Abstract: Caveolin-1 (CAV1) has long been implicated in cancer progression, and while widely accepted as an oncogenic protein, CAV1 also has tumor suppressor activity. CAV1 was first identified in an early study as the primary substrate of Src kinase, a potent ... ...

    Abstract Caveolin-1 (CAV1) has long been implicated in cancer progression, and while widely accepted as an oncogenic protein, CAV1 also has tumor suppressor activity. CAV1 was first identified in an early study as the primary substrate of Src kinase, a potent oncoprotein, where its phosphorylation correlated with cellular transformation. Indeed, CAV1 phosphorylation on tyrosine-14 (Y14; pCAV1) has been associated with several cancer-associated processes such as focal adhesion dynamics, tumor cell migration and invasion, growth suppression, cancer cell metabolism, and mechanical and oxidative stress. Despite this, a clear understanding of the role of Y14-phosphorylated pCAV1 in cancer progression has not been thoroughly established. Here, we provide an overview of the role of Src-dependent phosphorylation of tumor cell CAV1 in cancer progression, focusing on pCAV1 in tumor cell migration, focal adhesion signaling and metabolism, and in the cancer cell response to stress pathways characteristic of the tumor microenvironment. We also discuss a model for Y14 phosphorylation regulation of CAV1 effector protein interactions via the caveolin scaffolding domain.
    MeSH term(s) Animals ; Caveolin 1/metabolism ; Cell Movement/physiology ; Disease Progression ; Focal Adhesions/metabolism ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Phosphorylation ; Tyrosine/metabolism ; src-Family Kinases/metabolism
    Chemical Substances Caveolin 1 ; Tyrosine (42HK56048U) ; src-Family Kinases (EC 2.7.10.2)
    Language English
    Publishing date 2020-05-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 604857-2
    ISSN 1573-7233 ; 0167-7659
    ISSN (online) 1573-7233
    ISSN 0167-7659
    DOI 10.1007/s10555-020-09892-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1812: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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    ab Jg. 2022: Lesesaal (EG)

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