Cysteine Oxidation Promotes Dimerization/Oligomerization of Circadian Protein Period 2

Abstract

The molecular circadian clock is based on a transcriptional/translational feedback loop in which the stability and half-life of circadian proteins is of importance. Cysteine residues of proteins are subject to several redox reactions leading to S-thiolation and disulfide bond formation, altering protein stability and function. In this work, the ability of the circadian protein period 2 (PER2) to undergo oxidation of cysteine thiols was investigated in HEK-293T cells. PER2 includes accessible cysteines susceptible to oxidation by nitroso cysteine (CysNO), altering its stability by decreasing its monomer form and subsequently increasing PER2 homodimers and multimers. These changes were reversed by treatment with 2-mercaptoethanol and partially mimicked by hydrogen peroxide. These results suggest that cysteine oxidation can prompt PER2 homodimer and multimer formation in vitro, likely by S-nitrosation and disulphide bond formation. These kinds of post-translational modifications of PER2 could be part of the redox regulation of the molecular circadian clock.

Redox Regulation of Protein Functioning

“…One of the mechanisms of molecular circadian clock functioning is based on the half-life of circadian proteins. In their work, Baidanoff et al [ 5 ] investigated the ability of circadian protein period 2 (PER2) to undergo oxidation of thiol groups of cysteine. In this work, the authors showed that cysteine oxidation of PER2 results in the formation of homodimers and multimers in HEK-293T cells.…”