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Sökning: id:"swepub:oai:DiVA.org:umu-179525" > JAK3 Is Expressed i...

JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL).

Vadivel, Chella Krishna (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Gluud, Maria (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Torres-Rusillo, Sara (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
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Boding, Lasse (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Willerslev-Olsen, Andreas (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Buus, Terkild B. (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Nielsen, Tea Kirkegaard (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Persson, Jenny L., Professor (författare)
Malmö universitet,Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Biomedical Sciences, Malmö University, 21428 Malmö, Sweden,Institutionen för biomedicinsk vetenskap (BMV),Division of Basal Tumor Biology, Department of Molecular Biology, Umea University, 90187 Umea, Sweden
Bonefeld, Charlotte M. (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Geisler, Carsten (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Krejsgaard, Thorbjorn (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Fuglsang, Anja T. (författare)
Department of Plant and Environmental Sciences, University of Copenhagen, 1871 Frederiksberg, Denmark
Odum, Niels (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Woetmann, Anders (författare)
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
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 (creator_code:org_t)
2021-01-14
2021
Engelska.
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2
Relaterad länk:
https://doi.org/10.3...
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https://www.mdpi.com...
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https://urn.kb.se/re...
https://doi.org/10.3...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2Rγc located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with Sézary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro-an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

JAK3
Mycosis fungoides
Sézary syndrome
cutaneous T cell lymphoma
tyrosine kinases

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