21 May 2007

Nature Cell Biology doi: 10.1038/ncb1597

A protein known as caspase-14 has been identified as the enzyme involved in the protection of the skin against UVB damage and water loss, according to a study published online this week in Nature Cell Biology.

The involvement of caspase-family members in programmed cell death and inflammation is well understood, but a function for caspase-14 had previously not been identified. Using caspase-14 knockout mice, Wim Declercq and colleagues show that caspase-14 is responsible for the initial processing of profillagrin to fillagrin. Fillagrin is responsible for aggregating keratin and other proteins in the upper layers of the epidermis to form the stratum corneum – a layer of flattened dead-cell remnants that creates a protective barrier for the skin. The controlled processing of profillagrin to produce fillagrin ultimately maintains the integrity of the epidermis. In mice lacking caspase-14, their skin exhibits a defective stratum corneum and is more sensitive to water loss and UVB photodamage.

The identification of caspase-14 and its role in skin-barrier formation opens avenues for the pharmaceutical manipulation of this process to prevent the damage induced by UVB, the primary agent responsible for sunburn and skin ageing.

21 May 2007

Nature Cell Biology doi: 10.1038/ncb1589

A study in the June issue of Nature Cell Biology investigates how pluripotency, the ability of a stem cell to differentiate into every cell type of the adult organism, is regulated.

Understanding how stem cells maintain their pluripotent state has involved the characterisation of a multitude of transcription factors – the proteins that determine whether a specific gene is expressed or not. Pluripotency in embryonic stem cells was thought to be controlled primarily by the transcription factors Oct3/4 and Sox2, as these proteins were believed to activate Oct-Sox enchancers – regulatory regions that determine the expression of pluripotent stem cell-specific genes. Shinji Masui and colleagues used mutant mice lacking the Sox2 gene to show that although Sox2 is needed for stem cell pluripotency, it is not required for the enchancers to function and in fact governs the expression of Oct3/4. The authors went on to show that this regulation is indirect, as Sox2 controls the expression of a number of transcription factors that in turn regulate Oct3/4 expression.

This study illustrates the precise regulation of pluripotency by key proteins, and reorders the hierarchy of these factors with Sox2 as the master regulator — another small step towards a complete understanding of stem cell biology.