4.5 Article

Genotype-specific cortisol production associated with Cushing's syndrome adenoma with PRKACA mutations

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PKA Cα subunit mutation triggers caspase-dependent RIIβ subunit degradation via Ser114 phosphorylation

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Summary: Mutations in the PRKACA gene are a common cause of cortisol-producing adrenocortical adenomas and Cushing's syndrome, affecting the binding of regulatory subunits and leading to reduced RII β protein levels. The study shows that phosphorylation of RII β at Ser(114) is necessary for its degradation, mediated by caspase 16, resulting in increased cortisol secretion in adrenocortical cells. These findings provide insight into the molecular mechanisms and pathophysiological relevance of R subunit degradation caused by PRKACA mutations in adrenal Cushing's syndrome.

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