Identification of short protein-destabilizing sequences in Arabidopsis cyclin-dependent kinase inhibitors, ICKs.

This article focuses on the identification and characterization of short protein-destabilizing sequences within Arabidopsis cyclin-dependent kinase (CDK) inhibitors known as interactors/inhibitors of CDK (ICKs) or Kip-related proteins (KRPs). The study demonstrates that multiple short sequences, primarily located in the diverse N-terminal regions of ICKs, strongly reduce the stability and levels of fusion proteins in plants, yeast, and Escherichia coli, suggesting a conserved mechanism of protein destabilization. Computational analyses reveal that ICK proteins are largely intrinsically disordered except for a conserved C-terminal region, and some destabilizing sequences likely promote degradation through structural disorder rather than ubiquitin-dependent pathways. These findings indicate that both ubiquitin-dependent and ubiquitin-independent mechanisms regulate ICK protein levels, with implications for broader understanding of protein stability regulation in plants and potential applications in targeted protein degradation technologies.