Barrick Doug
T. C. Jenkins Department of Biophysics, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218, USA.
ACS Chem Biol. 2009 Jan 16;4(1):19-22. doi: 10.1021/cb900003f.
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.
通过模拟含五个锚蛋白重复序列的肿瘤抑制因子p19(INK4d)的磷酸化，天然状态可被破坏到在生理温度下仅存在部分折叠状态的程度。这种部分折叠状态模拟了在锚蛋白重复序列1和2中缺乏结构的一条折叠途径上的中间体，其比亲本构建体更快速地被泛素化。因此，p19(INK4d)的磷酸化可能通过生化（蛋白酶体）和生物物理（折叠以及与细胞周期蛋白依赖性激酶结合）机制来调节细胞周期进程。
