The proteasome maturation protein POMP increases proteasome assembly and activity in psoriatic lesional skin
Autor: | Mohamed Jemaà, Laurent Henry, Thierry Lavabre-Bertrand, Pierre-Emmanuel Stoebner, Matthieu Lacroix, Laurent Meunier, Barbara A. Zieba, Olivier Coux |
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Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes) |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Keratinocytes Cytoplasm Proteasome Endopeptidase Complex Cellular differentiation Biopsy Blotting Western Apoptosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology Dermatology Biology Biochemistry Cell Line 03 medical and health sciences Gene expression medicine Humans Psoriasis RNA Messenger RNA Small Interfering Molecular Biology Involucrin ComputingMilieux_MISCELLANEOUS Cell Proliferation integumentary system Cell Differentiation Molecular biology 3. Good health Cell biology Native Polyacrylamide Gel Electrophoresis HaCaT 030104 developmental biology medicine.anatomical_structure Proteasome Epidermal Cells Proteasome assembly Proteasome maturation protein RNA Interference Epidermis Keratinocyte Molecular Chaperones |
Zdroj: | Journal of Dermatological Science Journal of Dermatological Science, Elsevier, 2017, 88 (1), pp.10--19. ⟨10.1016/j.jdermsci.2017.04.009⟩ |
ISSN: | 1873-569X 0923-1811 |
Popis: | Background The ubiquitin proteasome pathway is involved in the pathogenesis of psoriasis and proteasome subunits are increased in lesional psoriatic skin. Recent works have highlighted that proteasome levels can be regulated through modulation of proteasome assembly notably by the proteasome maturation protein POMP. Objectives To investigate whether proteasome assembly and POMP expression are modified in psoriatic skin. Methods Proteasome assembly as well as expression of proteasome regulators were assessed in non-lesional and lesional psoriatic skin using native gel electrophoresis and western blots respectively. The protein and mRNA expression levels of POMP were compared by western blots, immunohistochemistry and quantitative polymerase chain reaction. The role of POMP in keratinocyte proliferation and differentiation was assessed by silencing POMP gene expression by RNA interference in human immortalized keratinocyte HaCaT cells. Results Both 20S and 26S proteasomes (and their respective proteolytic activities) as well as the main proteasome regulators are increased in lesional psoriatic skin. POMP binds to 20S precursor complexes and is overexpressed in lesional epidermal psoriatic skin, supporting that POMP-mediated proteasome assembly is increased in psoriatic skin. POMP silencing inhibited HaCaT cell proliferation and induced apoptosis through the inhibition of the proteasome assembly. Moreover POMP partial depletion decreased the expression of the differentiation markers keratin 10 and involucrin during the [Ca 2+ ]-induced HaCaT cells differentiation. Conclusion Altogether these results establish a potential role for POMP and proteasome assembly in psoriasis pathogenesis. |
Databáze: | OpenAIRE |
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