Biological regulation via ankyrin repeat folding.
By mimicking the phosphorylation of p19(INK4d), a tumor suppressor containing five ankyrin repeats, the native state could be destabilized to such an extent that only a partially folded state is populated at physiological temperature. This partly folded state, which mimics an on-pathway folding intermediate lacking structure in ankyrin repeats 1 and 2, is more rapidly ubiquitinated than the parent construct. Thus, phosphorylation of p19(INK4d) is likely to regulate cell-cycle progression through both biochemical (proteasomal) and biophysical (folding and binding to cyclin-dependent kinases) mechanisms.
Barrick
Doug
D
T. C. Jenkins Department of Biophysics, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA. barrick@jhu.edu
D017089:Ankyrin Repeat; D002453:Cell Cycle; D045744:Cell Line, Tumor; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050764:Cyclin-Dependent Kinase Inhibitor p19 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding
D050764:Cyclin-Dependent Kinase Inhibitor p19; D051361:Cyclin-Dependent Kinase 6