| Summary: | <p>The epidermis of skin is an essential barrier that protects the body from external stresses and
retains internal body fluids. The fine balance between cell proliferation, differentiation and
apoptosis as well as a well-coordinated immune response is vital in maintaining a healthy skin
barrier. The iASPP protein is inhibitor of p53-mediated apoptosis and can potentially function
as a proto-oncogene in tumourigenesis. Recent research has also demonstrated the regulatory
role of iASPP on the transcriptional activity of p63 in mediating proper epidermal stratification.
Furthermore, early data has suggested that iASPP could inhibit the DNA binding activity of the
NF-kB transcription factor p65 which is critical in controlling inflammatory gene expression.
The aim of this project was to investigate the autonomous role of epidermal iASPP in
epidermal development and homeostasis using an in vivo transgenic mouse model system.
Moreover, the role of epidermal iASPP in chemically induced skin carcinogenesis, and the
possible interaction between iASPP and p65 in keratinocytes were examined. </p>
<p>Transgenic mice with epidermal specific iASPP deletion (K14-iASPP-/-) exhibited wavy coat and
open eyelid phenotype similar to that observed in the total knockout model. K14-iASPP-/- mice
showed focal epidermal thickenings, with signs of immune cell infiltrates in the dermis.
Interestingly K14-iASPP-deficient mice were more susceptible to DMBA/TPA induced skin
carcinogenesis, and had significantly higher papilloma burden with early onset of papilloma
development compared to the wild type. Primary keratinocytes expressed higher levels of
inflammatory mediators in the absence of iASPP, and abnormal expression of such mediators
was detected in the K14-iASPP-/- mouse epidermis.</p>
<p>These results suggest that epidermal iASPP deficiency provided an inflammatory
microenvironment that supports the development of papillomas. Therefore epidermal iASPP
plays a key role in maintaining normal skin immunohomeostasis and offering protection
against chemically induced skin carcinogenesis. Further research is required to decipher the
molecular mechanisms by which iASPP modulates inflammatory signalling pathways.</p>
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