REGULATION OF CYCLIN-CDK ACTIVITY BY INOSITOL PYROPHOSPHATES
April 20th, 2007
Authors Erin K. O'Shea (left) and
Lee et al. recently defined a new role for the inositol polyphosphate IP7, which contains a pyrophosphate group (2 phosphates linked together) on one of the inositol ring positions. They demonstrated that IP7 regulates the activity of a cyclin-CDK-CDK inhibitor complex involved in relaying information about availability of the nutrient inorganic phosphate. This finding resolves a longstanding question about how cells communicate information about phosphate availability to a cyclin-CDK complex that is a central player in the phosphate-responsive signaling pathway. In response to starvation for phosphate, cells increase IP7 levels and IP7 binds to the cyclin-CDK-CDK inhibitor complex and inactivates its kinase activity. This inhibition is a key regulatory step, because it allows the transcription factor Pho4, a substrate for the cyclin-CDK complex, to be unphosphorylated and thereby turn on expression of phosphate-responsive genes.
This work demonstrates a new mechanism for regulating cyclin-CDK activity, and also provides a glimpse of the complex metabolic network that underlies phosphate sensing and signaling. Given the conservation of inositol polyphosphates, it is probable that inositol polyphosphates regulate many other biological processes.
article title: Regulation of a Cyclin-CDK-CDK Inhibitor Complex by Inositol Pyrophosphates