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    Sharpin SHANK-associated RH domain interacting protein [ Mus musculus (house mouse) ]

    Gene ID: 106025, updated on 27-Nov-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.

    Mechanistic insights into the homo-dimerization of HOIL-1L and SHARPIN.
    Zhang Y, Xu X, Wang Y, Wang Y, Zhou X, Pan L.

    12/1/2023
    Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death.

    Immune dysregulation in SHARPIN-deficient mice is dependent on CYLD-mediated cell death.
    Ang RL, Chan M, Legarda D, Sundberg JP, Sun SC, Gillespie VL, Chun N, Heeger PS, Xiong H, Lira SA, Ting AT., Free PMC Article

    01/8/2022
    A novel role for SHARPIN in amyloid-beta phagocytosis and inflammation by peripheral blood-derived macrophages in Alzheimer's disease.

    A novel role for SHARPIN in amyloid-β phagocytosis and inflammation by peripheral blood-derived macrophages in Alzheimer's disease.
    Krishnan D, Menon RN, Mathuranath PS, Gopala S.

    01/16/2021
    Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.

    Keratinocyte-specific deletion of SHARPIN induces atopic dermatitis-like inflammation in mice.
    Sundberg JP, Pratt CH, Goodwin LP, Silva KA, Kennedy VE, Potter CS, Dunham A, Sundberg BA, HogenEsch H., Free PMC Article

    09/12/2020
    The sharpin may complex with both kindlin-1 and the integrin beta1 CT to restrict the talin head domain binding, thus inhibiting beta1-integrin activation.

    Sharpin suppresses β1-integrin activation by complexing with the β1 tail and kindlin-1.
    Gao J, Bao Y, Ge S, Sun P, Sun J, Liu J, Chen F, Han L, Cao Z, Qin J, White GC, Xu Z, Ma YQ., Free PMC Article

    09/12/2020
    Fibroblasts derived from Sharpin(cpdm)Myd88(--) mice failed to provide protection against TNF-induced cell death. Sharpin(cpdm)Myd88(--) mice had reduced TNF production in their skin.

    Innate immune adaptor MyD88 deficiency prevents skin inflammation in SHARPIN-deficient mice.
    Sharma BR, Karki R, Lee E, Zhu Q, Gurung P, Kanneganti TD., Free PMC Article

    06/6/2020
    SHARPIN, a protein previously associated with increased cancer growth and metastasis, may also have important regulatory roles in controlling the tumor microenvironment

    (68)Ga-DOTA-E[c(RGDfK)](2) PET Imaging of SHARPIN-Regulated Integrin Activity in Mice.
    Siitonen R, Peuhu E, Autio A, Liljenbäck H, Mattila E, Metsälä O, Käkelä M, Saanijoki T, Dijkgraaf I, Jalkanen S, Ivaska J, Roivainen A., Free PMC Article

    04/18/2020
    LUBAC-tethering motifs (LTMs) located N terminally to the UBL domains of HOIL-1L and SHARPIN heterodimerize and fold into a single globular domain.

    Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization.
    Fujita H, Tokunaga A, Shimizu S, Whiting AL, Aguilar-Alonso F, Takagi K, Walinda E, Sasaki Y, Shimokawa T, Mizushima T, Ohki I, Ariyoshi M, Tochio H, Bernal F, Shirakawa M, Iwai K., Free PMC Article

    10/5/2019
    Data show that keratinocyte-specific deletion of ubiquitin-protein ligases HOIP, HOIL-1 (E-KO) and shank-interacting protein-like 1 protein (SHARPIN) results in severe dermatitis causing postnatal lethality.

    LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L.
    Taraborrelli L, Peltzer N, Montinaro A, Kupka S, Rieser E, Hartwig T, Sarr A, Darding M, Draber P, Haas TL, Akarca A, Marafioti T, Pasparakis M, Bertin J, Gough PJ, Bouillet P, Strasser A, Leverkus M, Silke J, Walczak H., Free PMC Article

    01/19/2019
    Both Sharpin/Fas and Sharpin/Fasl compound mutant mice developed an auto-inflammatory phenotype similar to that seen in Sharpin null mice, indicating that initiation of apoptosis by FAS signalling is likely not involved in the pathogenesis of this disease.

    Loss of FAS/FASL signalling does not reduce apoptosis in Sharpin null mice.
    Potter CS, Silva KA, Kennedy VE, Stearns TM, HogenEsch H, Sundberg JP., Free PMC Article

    07/14/2018
    results altogether demonstrate distinct roles of SHARPIN in initiating systemic inflammation and dermatitis. Furthermore, skin inflammation in Sharpin(cpdm) mice is specifically modulated by IL-1beta, highlighting the importance of specific targeted therapies in the IL-1 signaling blockade.

    Distinct role of IL-1β in instigating disease in Sharpin(cpdm) mice.
    Gurung P, Sharma BR, Kanneganti TD., Free PMC Article

    05/5/2018
    Itgb1 inhibition alleviates the chronic hyperproliferative dermatitis phenotype of Sharpin-deficient mice.

    Integrin beta 1 inhibition alleviates the chronic hyperproliferative dermatitis phenotype of SHARPIN-deficient mice.
    Peuhu E, Salomaa SI, De Franceschi N, Potter CS, Sundberg JP, Pouwels J., Free PMC Article

    11/4/2017
    LUBAC components control TLR3-mediated innate immunity, thereby preventing development of immunodeficiency and autoinflammation.

    --LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation.
    Zinngrebe J, Rieser E, Taraborrelli L, Peltzer N, Hartwig T, Ren H, Kovács I, Endres C, Draber P, Darding M, von Karstedt S, Lemke J, Dome B, Bergmann M, Ferguson BJ, Walczak H., Free PMC Article

    08/12/2017
    Suppression of SHARPIN impaired cell proliferation, angiogenesis, and invasion and reduced levels of MMP-9 in Prostate cancer cells and reduced the size of Metastatic Lung tumors induced by these cells in mice.

    Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals.
    Huang H, Du T, Zhang Y, Lai Y, Li K, Fan X, Zhu D, Lin T, Xu K, Huang J, Liu L, Guo Z.

    07/22/2017
    Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal extracellular matrix.

    SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.
    Peuhu E, Kaukonen R, Lerche M, Saari M, Guzmán C, Rantakari P, De Franceschi N, Wärri A, Georgiadou M, Jacquemet G, Mattila E, Virtakoivu R, Liu Y, Attieh Y, Silva KA, Betz T, Sundberg JP, Salmi M, Deugnier MA, Eliceiri KW, Ivaska J., Free PMC Article

    07/15/2017
    Study found that the NZF domain of SHARPIN, but not that of HOIL-1L, is critical for effective protection from programmed cell death by enhancing the recruitment of the linear ubiquitin chain assembly complex to the activated TNFR complex. The binding activity to K63-linked ubiquitin chains that the NZF domain of SHARPIN, but not that of HOIL-1L, possesses appears to be involved in the recruitment.

    Differential Involvement of the Npl4 Zinc Finger Domains of SHARPIN and HOIL-1L in Linear Ubiquitin Chain Assembly Complex-Mediated Cell Death Protection.
    Shimizu S, Fujita H, Sasaki Y, Tsuruyama T, Fukuda K, Iwai K., Free PMC Article

    05/27/2017
    this study reveals a critical function of SHARPIN in TCR-induced NF-kappaB and JNK signalling and thymic Treg cell generation

    SHARPIN controls the development of regulatory T cells.
    Redecke V, Chaturvedi V, Kuriakose J, Häcker H., Free PMC Article

    05/6/2017
    SHARPIN-deficient mice develop a chronic proliferative dermatitis presenting angiogenesis and lymphatic dilatation.

    Angiogenesis in the skin of SHARPIN-deficient mice with chronic proliferative dermatitis.
    HogenEsch H, Sola M, Stearns TM, Silva KA, Kennedy VE, Sundberg JP., Free PMC Article

    04/29/2017
    Study identifies a role for SHARPIN in TCR signaling whereby it maintains immunological homeostasis and tolerance by regulating Treg cells.

    SHARPIN controls regulatory T cells by negatively modulating the T cell antigen receptor complex.
    Park Y, Jin HS, Lopez J, Lee J, Liao L, Elly C, Liu YC., Free PMC Article

    07/16/2016
    severity of the esophagitis was not affected by crossing SHARPIN-deficient mice with lymphocyte-deficient Rag1 null mice

    The pathogenesis of chronic eosinophilic esophagitis in SHARPIN-deficient mice.
    Chien SJ, Silva KA, Kennedy VE, HogenEsch H, Sundberg JP., Free PMC Article

    04/23/2016
    Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.

    Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.
    Jeschke A, Catala-Lehnen P, Sieber S, Bickert T, Schweizer M, Koehne T, Wintges K, Marshall RP, Mautner A, Duchstein L, Otto B, Horst AK, Amling M, Kreienkamp HJ, Schinke T.

    01/2/2016
    Data indicate that genetic ablation of caspase-1 and -11 from cpdm mice significantly reduced skin inflammation in sharpin-deficient mice.

    The Inflammatory Caspases-1 and -11 Mediate the Pathogenesis of Dermatitis in Sharpin-Deficient Mice.
    Douglas T, Champagne C, Morizot A, Lapointe JM, Saleh M.

    12/19/2015
    Our results suggest that SHARPIN plays a significant role in skeletal homeostasis and that this role is strongly regulated through TNF pathways.

    Sharpin is a key regulator of skeletal homeostasis in a TNF-dependent manner.
    McGowan HW, Schuijers JA, Grills BL, McDonald SJ, Rickard JA, Silke J, McDonald AC.

    08/29/2015
    Tnfr1, but not Tnfr2, deficiency suppresses inflammation in sharpin deficient mice.

    TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice.
    Rickard JA, Anderton H, Etemadi N, Nachbur U, Darding M, Peltzer N, Lalaoui N, Lawlor KE, Vanyai H, Hall C, Bankovacki A, Gangoda L, Wong WW, Corbin J, Huang C, Mocarski ES, Murphy JM, Alexander WS, Voss AK, Vaux DL, Kaiser WJ, Walczak H, Silke J., Free PMC Article

    07/25/2015
    Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis.

    Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis.
    Kumari S, Redouane Y, Lopez-Mosqueda J, Shiraishi R, Romanowska M, Lutzmayer S, Kuiper J, Martinez C, Dikic I, Pasparakis M, Ikeda F., Free PMC Article

    07/25/2015
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