English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

The p63 transcription factor, homolog to the p53 tumor suppressor gene, plays a crucial role in epidermal and limb development, as its mutations are associated to human congenital syndromes characterized by skin, craniofacial and limb defects. While limb and skin-specific p63 transcriptional targets are being discovered, little is known of the post-translation modifications controlling ΔNp63 α  functions. Here we show that the p300 acetyl-transferase physically interacts  in vivo  with ΔNp63 α  and catalyzes its acetylation on lysine 193 (K193) inducing ΔNp63 α  stabilization and activating specific transcriptional functions. Furthermore we show that Fibroblast Growth Factor-8 (FGF8), a morphogenetic signaling molecule essential for embryonic limb development, increases the binding of ΔNp63 α  to the tyrosine kinase c-Abl as well as the levels of ΔNp63 α  acetylation. Notably, the natural mutant ΔNp63 α -K193E, associated to the Split-Hand/Foot Malformation-IV syndrome, cannot be acetylated by this pathway. This mutant ΔNp63 α  protein displays promoter-specific loss of DNA binding activity and consequent altered expression of development-associated ΔNp63 α  target genes. Our results link FGF8, c-Abl and p300 in a regulatory pathway that controls ΔNp63 α  protein stability and transcriptional activity. Hence, limb malformation-causing p63 mutations, such as the K193E mutation, are likely to result in aberrant limb development via the combined action of altered protein stability and altered promoter occupancy.

FGF8, c-Abl and p300 participate in a pathway that controls stability and function of the ΔNp63 α protein