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  1. Article ; Online: Yeast derlin Dfm1 employs a chaperone-like function to resolve misfolded membrane protein stress.

    Kandel, Rachel / Jung, Jasmine / Syau, Della / Kuo, Tiffany / Songster, Livia / Horn, Casey / Chapman, Claire / Aguayo, Analine / Duttke, Sascha / Benner, Christopher / Neal, Sonya E

    PLoS biology

    2023  Volume 21, Issue 1, Page(s) e3001950

    Abstract: Protein aggregates are a common feature of diseased and aged cells. Membrane proteins comprise a quarter of the proteome, and yet, it is not well understood how aggregation of membrane proteins is regulated and what effects these aggregates can have on ... ...

    Abstract Protein aggregates are a common feature of diseased and aged cells. Membrane proteins comprise a quarter of the proteome, and yet, it is not well understood how aggregation of membrane proteins is regulated and what effects these aggregates can have on cellular health. We have determined in yeast that the derlin Dfm1 has a chaperone-like activity that influences misfolded membrane protein aggregation. We establish that this function of Dfm1 does not require recruitment of the ATPase Cdc48 and it is distinct from Dfm1's previously identified function in dislocating misfolded membrane proteins from the endoplasmic reticulum (ER) to the cytosol for degradation. Additionally, we assess the cellular impacts of misfolded membrane proteins in the absence of Dfm1 and determine that misfolded membrane proteins are toxic to cells in the absence of Dfm1 and cause disruptions to proteasomal and ubiquitin homeostasis.
    MeSH term(s) Membrane Proteins/metabolism ; Molecular Chaperones/metabolism ; Protein Folding ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Dfm1 protein, S cerevisiae ; Membrane Proteins ; Molecular Chaperones ; Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2023-01-23
    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 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3001950
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion to enable the retrotranslocation of ERAD membrane substrates.

    Nejatfard, Anahita / Wauer, Nicholas / Bhaduri, Satarupa / Conn, Adam / Gourkanti, Saroj / Singh, Narinderbir / Kuo, Tiffany / Kandel, Rachel / Amaro, Rommie E / Neal, Sonya E

    Cell reports

    2022  Volume 38, Issue 12, Page(s) 110578

    Language English
    Publishing date 2022-02-23
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2022.110578
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Derlin rhomboid pseudoproteases employ substrate engagement and lipid distortion to enable the retrotranslocation of ERAD membrane substrates.

    Nejatfard, Anahita / Wauer, Nicholas / Bhaduri, Satarupa / Conn, Adam / Gourkanti, Saroj / Singh, Narinderbir / Kuo, Tiffany / Kandel, Rachel / Amaro, Rommie E / Neal, Sonya E

    Cell reports

    2021  Volume 37, Issue 3, Page(s) 109840

    Abstract: Nearly one-third of proteins are initially targeted to the endoplasmic reticulum (ER) membrane, where they are correctly folded and then delivered to their final cellular destinations. To prevent the accumulation of misfolded membrane proteins, ER- ... ...

    Abstract Nearly one-third of proteins are initially targeted to the endoplasmic reticulum (ER) membrane, where they are correctly folded and then delivered to their final cellular destinations. To prevent the accumulation of misfolded membrane proteins, ER-associated degradation (ERAD) moves these clients from the ER membrane to the cytosol, a process known as retrotranslocation. Our recent work in Saccharomyces cerevisiae reveals a derlin rhomboid pseudoprotease, Dfm1, is involved in the retrotranslocation of ubiquitinated ERAD membrane substrates. In this study, we identify conserved residues of Dfm1 that are critical for retrotranslocation. We find several retrotranslocation-deficient Loop 1 mutants that display impaired binding to membrane substrates. Furthermore, Dfm1 possesses lipid thinning function to facilitate in the removal of ER membrane substrates, and this feature is conserved in its human homolog, Derlin-1, further implicating that derlin-mediated retrotranslocation is a well-conserved process.
    MeSH term(s) Endoplasmic Reticulum-Associated Degradation ; Lipid Metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mutation ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Transport ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Valosin Containing Protein/genetics ; Valosin Containing Protein/metabolism
    Chemical Substances DER1 protein, S cerevisiae ; Dfm1 protein, S cerevisiae ; Membrane Proteins ; Saccharomyces cerevisiae Proteins ; CDC48 protein, S cerevisiae (EC 3.6.4.-) ; Valosin Containing Protein (EC 3.6.4.6)
    Language English
    Publishing date 2021-10-20
    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. ; Video-Audio Media
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109840
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine

    Kuo, Tiffany / Christine Wang / Lbachir BenMohamed / Sravya Chilukuri / Tina Badakhshan

    Vaccine. 2014 Nov. 28, v. 32, no. 50

    2014  

    Abstract: Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 ... ...

    Abstract Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries, their development has been difficult. During the most recent National Institute of Health (NIH) workshop titled “Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities”, basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or a whole viral protein, which contain both “pathogenic symptomatic” and “protective asymptomatic” antigens and epitopes. In this report, we continue to advocate developing “asymptomatic” epitope-based sub-unit vaccine strategies that selectively incorporate “protective asymptomatic” epitopes which: (i) are exclusively recognized by effector memory CD4+ and CD8+ T cells (TEM cells) from “naturally” protected seropositive asymptomatic individuals; and (ii) protect human leukocyte antigen (HLA) transgenic animal models of ocular and genital herpes. We review the role of animal models in herpes vaccine development and discuss their current status, challenges, and prospects.
    Keywords animal models ; CD4-positive T-lymphocytes ; CD8-positive T-lymphocytes ; death ; encephalitis ; epitopes ; funding ; herpes simplex ; HLA antigens ; Human herpesvirus 1 ; neonates ; seroprevalence ; transgenic animals ; transmission electron microscopy ; vaccine development ; vaccines ; viruses
    Language English
    Dates of publication 2014-1128
    Size p. 6733-6745.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2014.10.002
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine.

    Kuo, Tiffany / Wang, Christine / Badakhshan, Tina / Chilukuri, Sravya / BenMohamed, Lbachir

    Vaccine

    2014  Volume 32, Issue 50, Page(s) 6733–6745

    Abstract: Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 ... ...

    Abstract Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) infections have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a billion individuals worldwide. HSV-1 infections are predominant than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries, their development has been difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One "common denominator" among previously failed clinical herpes vaccine trials is that they either used a whole virus or a whole viral protein, which contain both "pathogenic symptomatic" and "protective asymptomatic" antigens and epitopes. In this report, we continue to advocate developing "asymptomatic" epitope-based sub-unit vaccine strategies that selectively incorporate "protective asymptomatic" epitopes which: (i) are exclusively recognized by effector memory CD4(+) and CD8(+) T cells (TEM cells) from "naturally" protected seropositive asymptomatic individuals; and (ii) protect human leukocyte antigen (HLA) transgenic animal models of ocular and genital herpes. We review the role of animal models in herpes vaccine development and discuss their current status, challenges, and prospects.
    MeSH term(s) Drug Discovery/methods ; Epitopes, T-Lymphocyte/immunology ; Herpes Genitalis/epidemiology ; Herpes Genitalis/prevention & control ; Herpes Simplex/epidemiology ; Herpes Simplex/prevention & control ; Herpesvirus Vaccines/immunology ; Herpesvirus Vaccines/isolation & purification ; Humans ; Models, Animal ; Simplexvirus/immunology
    Chemical Substances Epitopes, T-Lymphocyte ; Herpesvirus Vaccines
    Language English
    Publishing date 2014-11-28
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2014.10.002
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  6. Article: Oxygen Tension and Riboflavin Gradients Cooperatively Regulate the Migration of

    Kim, Beum Jun / Chu, Injun / Jusuf, Sebastian / Kuo, Tiffany / TerAvest, Michaela A / Angenent, Largus T / Wu, Mingming

    Frontiers in microbiology

    2016  Volume 7, Page(s) 1438

    Abstract: Shewanella ... ...

    Abstract Shewanella oneidensis
    Language English
    Publishing date 2016-09-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2016.01438
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Current trends in negative immuno-synergy between two sexually transmitted infectious viruses: HIV-1 and HSV-1/2.

    Chentoufi, Aziz Alami / Dervillez, Xavier / Rubbo, Pierre-Alain / Kuo, Tiffany / Zhang, Xiuli / Nagot, Nicolas / Tuaillon, Edouard / Van De Perre, Philippe / Nesburn, Anthony B / Benmohamed, Lbachir

    Current trends in immunology

    2012  Volume 13, Page(s) 51–68

    Abstract: In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and/or type 2 (HSV-1/2). An ... ...

    Abstract In the current era of effective anti-retroviral therapy, immuno-compromised patients with HIV-1 infection do live long enough to suffer diseases caused by many opportunistic infections, such as herpes simplex virus type 1 and/or type 2 (HSV-1/2). An estimated two-third of the 40 million individuals that have contracted HIV-1 worldwide are co-infected with HSV-1/2 viruses, the causative agents of ocular oro-facial and genital herpes. The highest prevalence of HIV and HSV-1/2 infections are confined to the same regions of Sub-Saharan Africa. HSV-1/2 infections affect HIV-1 immunity, and vice versa. While important research gains have been made in understanding herpes and HIV immunity, the cellular and molecular mechanisms underlying the crosstalk between HSV-1/2 and HIV co-infection remain to be fully elucidated. Understanding the mechanisms behind the apparent HSV/HIV negative immuno-synergy maybe the key to successful HSV and HIV vaccines; both are currently unavailable. An effective herpes immunotherapeutic vaccine would in turn - indirectly - contribute in reducing HIV epidemic. The purpose of this review is: (i) to summarize the current trends in understanding the negative immuno-crosstalk between HIV and HSV-1/2 infections; and (ii) to discuss the possibility of developing a novel mucosal herpes immunotherapeutic strategy or even a combined or chimeric immunotherapeutic vaccine that simultaneously targets HIV and HSV-1/2 infections. These new trends in immunology of HSV-1/2 and HIV co-infections should become part of current efforts in preventing sexually transmitted infections. The alternative is needed to balance the ethical and financial concerns associated with the rising number of unsuccessful mono-valent clinical vaccine trials.
    Language English
    Publishing date 2012-12-20
    Publishing country India
    Document type Journal Article
    ZDB-ID 2121311-2
    ISSN 0972-4567
    ISSN 0972-4567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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