Chronoregulation by Asparagine Deamidation
Steven J. Weintraub1* and
Benjamin E. Deverman2
1Division of Urology, Department of Cell Biology and Physiology, The Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8242, St. Louis, MO 63110, USA.
2Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
Gloss: The deamidation of an asparagine is a common posttranslational modification. When an asparagine in a protein undergoes deamidation, its amide side chain is nonenzymatically hydrolyzed, which results in the replacement of the asparagine residue with either an aspartate or an isoaspartate. By introducing a negative charge and isomerization into a protein in this manner, the deamidation of an asparagine has the potential to alter protein function. Asparagine deamidation is widely thought to be an unregulated process that is nothing more than a form of protein damage. However, it has been demonstrated that the inherent deamidation rate of an asparagine is actually tightly regulated by its surrounding sequence and that a wide range of deamidation rates can be genetically programmed into a protein simply by altering the amino acids in the sequence surrounding an asparagine. Because of this property, it was proposed 40 years ago that asparagine deamidation could serve as molecular timer that is genetically programmed to time biological processes. This STKE review, with 4 figures and 49 references, discusses the evidence in support of the molecular timer hypothesis.
*Corresponding author. E-mail: weintraub{at}wustl.edu
