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/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Small proline-rich protein 2A and 2D (SPRR2A and SPRR2D) provide barrier function in terminally differentiated stratified squamous epithelia through the epidermal differentiation complex. However, little is known how SPRR2A/2D expression is controlled and their role in chronic inflammation. Here, we showed that that SPRR2A/2D expression is controlled by a regulatory loop formed by RNA-binding protein RBM38 and tumor suppressor p73. Specifically, we found that SPRR2A/2D expression was induced by ectopic expression of RBM38 or p73 but suppressed by knockout of Rbm38 or p73. We also found that RBM38-mediated expression of SPRR2A/2D was p73-dependent and that induction of SPRR2A/2D during keratinocyte differentiation was dependent on both p73 and Rbm38. Additionally, we found that SPRR2A/2D expression was closely associated with p73 expression in normal and cancerous tissues. To determine the biological function of the RBM38-p73 loop potentially via SPRR2A/2D, we generated a cohort of wild-type, Rbm38 -/-  , Trp73 +/-  , and Rbm38 -/- ;Trp73 +/-  mice. We found that Rbm38 -/- ;Trp73 +/-  mice had a much shorter lifespan than that for Rbm38 -/-  -and to a lesser extent for Trp73 +/-  mice-but were less prone to spontaneous tumors than Trp73 +/-  or Rbm38 -/-  mice. We also found that Rbm38 -/- ;Trp73 +/-  mice exhibited weak expression of SPRR2A/2D in multiple tissues and were susceptible to systemic chronic inflammation, suggesting that decreased SPRR2A/2D expression is likely responsible for chronic inflammation in Rbm38 -/- ;Trp73 +/-  mice, leading to a shortened lifespan. Together, our data reveal that SPRR2A/2D are novel targets of the RBM38-p73 loop and contribute to p73-dependent suppression of chronic inflammation.

Small Proline-Rich Protein 2A and 2D Are Regulated by the RBM38-p73 Axis and Associated with p73-Dependent Suppression of Chronic Inflammation