Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 130, Issue 3, Pages 671-681Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jid.2009.327
Keywords
-
Categories
Funding
- Medical Research Council [G78/6810]
- Wellcome Trust [065362/Z/01/Z]
- Dystrophic Epidermolysis Research Association [LANE6]
- Cancer Research UK [C26/A1461, C26/A6694]
Ask authors/readers for more resources
The consequences of cell stress induced by misfolded proteins are an important contributor to many human diseases. One such disease is epidermolysis bullosa simplex (EBS), caused by mutations in the structural proteins (keratins K5 or K14) of the proliferative compartment of the epidermis (basal keratinocyte layer), leading to cell fragility and blistering. In severe EBS, the mutation is associated with aggregates of nonfilamentous keratin protein, and cell lines carrying Such mutations show a constitutively activated stress response. Analysis of the cellular mechanisms leading to cell breakdown on physical stress may point the way to mutation-independent therapeutic approaches to these incurable genetic disorders. We therefore subjected EBS cell lines, immortalized from patients with EBS, to an oscillating mechanical stress in assays designed to mimic the physical trauma that leads to cell breakdown in vivo. These experiments show that mechanical stress activates extracellular signal-regulated kinase (ERK) signaling in these cells, and that the keratin mutant cells also show a resistance to apoptosis following mechanical stress that is reversed by inhibiting ERK. The consequences of constitutive expression of large amounts of defective structural protein in a tissue cell must be properly understood for the development of safe and effective therapies for these disorders.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available