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  1. Article ; Online: Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice.

    Jarvis, Rebecca / Josephine Ng, Shu Fun / Nathanson, Anna J / Cardarelli, Ross A / Abiraman, Krithika / Wade, Fergus / Evans-Strong, Aidan / Fernandez-Campa, Marina P / Deeb, Tarek Z / Smalley, Joshua L / Jamier, Tanguy / Gurrell, Ian K / McWilliams, Lisa / Kawatkar, Aarti / Conway, Leslie C / Wang, Qi / Burli, Roland W / Brandon, Nicholas J / Chessell, Iain P /
    Goldman, Aaron J / Maguire, Jamie L / Moss, Stephen J

    Cell reports. Medicine

    2023  Volume 4, Issue 3, Page(s) 100957

    Abstract: Hyperpolarizing ... ...

    Abstract Hyperpolarizing GABA
    MeSH term(s) Mice ; Animals ; Benzodiazepines/pharmacology ; Benzodiazepines/therapeutic use ; Status Epilepticus/drug therapy ; Seizures/metabolism ; gamma-Aminobutyric Acid/metabolism ; Symporters/metabolism
    Chemical Substances Benzodiazepines (12794-10-4) ; gamma-Aminobutyric Acid (56-12-2) ; Symporters
    Language English
    Publishing date 2023-03-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2023.100957
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Developmental Regulation of KCC2 Phosphorylation Has Long-Term Impacts on Cognitive Function.

    Moore, Yvonne E / Conway, Leslie C / Wobst, Heike J / Brandon, Nicholas J / Deeb, Tarek Z / Moss, Stephen J

    Frontiers in molecular neuroscience

    2019  Volume 12, Page(s) 173

    Abstract: ... ...

    Abstract GABA
    Language English
    Publishing date 2019-07-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2019.00173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Inactive USP14 and inactive UCHL5 cause accumulation of distinct ubiquitinated proteins in mammalian cells.

    Chadchankar, Jayashree / Korboukh, Victoria / Conway, Leslie C / Wobst, Heike J / Walker, Chandler A / Doig, Peter / Jacobsen, Steve J / Brandon, Nicholas J / Moss, Stephen J / Wang, Qi

    PloS one

    2019  Volume 14, Issue 11, Page(s) e0225145

    Abstract: USP14 is a cysteine protease deubiquitinase associated with the proteasome and plays important catalytic and allosteric roles in proteasomal degradation. USP14 inhibition has been considered a therapeutic strategy for accelerating degradation of ... ...

    Abstract USP14 is a cysteine protease deubiquitinase associated with the proteasome and plays important catalytic and allosteric roles in proteasomal degradation. USP14 inhibition has been considered a therapeutic strategy for accelerating degradation of aggregation-prone proteins in neurodegenerative diseases and for inhibiting proteasome function to induce apoptotic cell death in cancers. Here we studied the effects of USP14 inhibition in mammalian cells using small molecule inhibitors and an inactive USP14 mutant C114A. Neither the inhibitors nor USP14 C114A showed consistent or significant effects on the level of TDP-43, tau or α-synuclein in HEK293T cells. However, USP14 C114A led to a robust accumulation of ubiquitinated proteins, which were isolated by ubiquitin immunoprecipitation and identified by mass spectrometry. Among these proteins we confirmed that ubiquitinated β-catenin accumulated in the cells expressing USP14 C114A with immunoblotting and immunoprecipitation experiments. The proteasome binding domain of USP14 C114A is required for its effect on ubiquitinated proteins. UCHL5 is the other cysteine protease deubiquitinase associated with the proteasome. Interestingly, the inactive mutant of UCHL5 C88A also caused an accumulation of ubiquitinated proteins in HEK293T cells but did not affect β-catenin, demonstrating USP14 but not UCHL5 has a specific effect on β-catenin. We used ubiquitin immunoprecipitation and mass spectrometry to identify the accumulated ubiquitinated proteins in UCHL5 C88A expressing cells which are mostly distinct from those identified in USP14 C114A expressing cells. Among the identified proteins are well established proteasome substrates and proteasome subunits. Besides β-catenin, we also verified with immunoblotting that UCHL5 C88A inhibits its own deubiquitination and USP14 C114A inhibits deubiquitination of two proteasomal subunits PSMC1 and PSMD4. Together our data suggest that USP14 and UCHL5 can deubiquitinate distinct substrates at the proteasome and regulate the ubiquitination of the proteasome itself which is tightly linked to its function.
    MeSH term(s) Binding Sites ; DNA-Binding Proteins/metabolism ; HEK293 Cells ; Humans ; Mass Spectrometry ; Mutation ; Proteasome Endopeptidase Complex/metabolism ; Small Molecule Libraries/pharmacology ; Ubiquitin Thiolesterase/chemistry ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism ; Ubiquitin Thiolesterase/pharmacology ; Ubiquitinated Proteins/metabolism ; Ubiquitination ; alpha-Synuclein/metabolism ; beta Catenin/metabolism
    Chemical Substances CTNNB1 protein, human ; DNA-Binding Proteins ; Small Molecule Libraries ; TARDBP protein, human ; USP14 protein, human ; Ubiquitinated Proteins ; alpha-Synuclein ; beta Catenin ; UCHL5 protein, human (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2019-11-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0225145
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: N

    Conway, Leslie C / Cardarelli, Ross A / Moore, Yvonne E / Jones, Karen / McWilliams, Lisa J / Baker, David J / Burnham, Matthew P / Bürli, Roland W / Wang, Qi / Brandon, Nicholas J / Moss, Stephen J / Deeb, Tarek Z

    The Journal of biological chemistry

    2017  Volume 292, Issue 52, Page(s) 21253–21263

    Abstract: ... ...

    Abstract K
    MeSH term(s) Animals ; Cell Membrane/metabolism ; Embryo, Mammalian ; Ethylmaleimide/metabolism ; Humans ; Membrane Transport Modulators/metabolism ; Neurons/metabolism ; Phosphorylation/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA/metabolism ; Symporters/metabolism ; Symporters/physiology ; K Cl- Cotransporters
    Chemical Substances Membrane Transport Modulators ; Receptors, GABA ; Symporters ; Ethylmaleimide (O3C74ACM9V)
    Language English
    Publishing date 2017-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M117.817841
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Molecular architecture of potassium chloride co-transporter KCC2.

    Agez, Morgane / Schultz, Patrick / Medina, Igor / Baker, David J / Burnham, Matthew P / Cardarelli, Ross A / Conway, Leslie C / Garnier, Kelly / Geschwindner, Stefan / Gunnarsson, Anders / McCall, Eileen J / Frechard, Alexandre / Audebert, Stéphane / Deeb, Tarek Z / Moss, Stephen J / Brandon, Nicholas J / Wang, Qi / Dekker, Niek / Jawhari, Anass

    Scientific reports

    2017  Volume 7, Issue 1, Page(s) 16452

    Abstract: KCC2 is a neuron specific ... ...

    Abstract KCC2 is a neuron specific K
    Language English
    Publishing date 2017-11-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-017-15739-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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