Paulina Hennig


Last Name

Hennig

First Name

Paulina

ORCID

0000-0003-2633-452X

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2019 - 201912020 - 20223
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Publications 1 - 4 of 4
  • Interaction of the NRF2 and p63 transcription factors promotes keratinocyte proliferation in the epidermis
    Item type: Journal Article
    Kurinna, Svitlana; Seltmann, Kristin; Bachmann, Andreas L.; et al. (2021)
    Nucleic Acids Research
    Epigenetic regulation of cell and tissue function requires the coordinated action of transcription factors. However, their combinatorial activities during regeneration remain largely unexplored. Here, we discover an unexpected interaction between the cytoprotective transcription factor NRF2 and p63- a key player in epithelial morphogenesis. Chromatin immunoprecipitation combined with sequencing and reporter assays identifies enhancers and promoters that are simultaneously activated by NRF2 and p63 in human keratinocytes. Modeling of p63 and NRF2 binding to nucleosomal DNA suggests their chromatin-assisted interaction. Pharmacological and genetic activation of NRF2 increases NRF2-p63 binding to enhancers and promotes keratinocyte proliferation, which involves the common NRF2-p63 target cyclin-dependent kinase 12. These results unravel a collaborative function of NRF2 and p63 in the control of epidermal renewal and suggest their combined activation as a strategy to promote repair of human skin and other stratified epithelia.
  • The NLRP1 Inflammasome Pathway Is Silenced in Cutaneous Squamous Cell Carcinoma
    Item type: Journal Article
    Sand, Jennifer; Fenini, Gabriele; Grossi, Serena; et al. (2019)
    Journal of Investigative Dermatology
  • Inactivation of the Cytoprotective Major Vault Protein by Caspase-1 and -9 in Epithelial Cells during Apoptosis
    Item type: Journal Article
    Grossi, Serena; Fenini, Gabriele; Kockmann, Tobias; et al. (2020)
    Journal of Investigative Dermatology
    Inflammasome activation induces caspase-1–dependent secretion of the proinflammatory cytokine IL-1β. In addition, caspase-1 activates the protein GSDMD in immune cells, causing pyroptosis, a lytic type of cell death. In contrast, UVB irradiation of human primary keratinocytes induces NLRP1 inflammasome activation, cytokine secretion, and caspase-1–dependent apoptosis, rather than pyroptosis. Here, we addressed the molecular mechanisms underlying the role of caspase-1 in UVB-induced cell death of human primary keratinocytes. We show that GSDMD is a poor substrate of caspase-1 in human primary keratinocytes and that its activation upon UVB irradiation supports secretion of IL-1β. We screened for novel substrates of caspase-1 by a mass spectrometry–based approach and identified the specific cleavage of the major vault protein (MVP) at D441 by caspase-1 and -9. MVP is the main component of vaults, highly conserved ribonucleoprotein particles, whose functions are poorly understood. Cleavage of MVP is a common event occurring in human primary keratinocytes and fibroblasts undergoing apoptosis induced by different stimuli. In contrast, MVP cleavage could not be detected in pyroptotic cells. Cleavage of MVP by caspase-1 and -9 inactivates this cytoprotective protein. These results demonstrate a proapoptotic activity of caspase-1 and a crosstalk with caspase-9 upon inactivation of the cytoprotective MVP in apoptotic epithelial cells.
Publications 1 - 4 of 4