UbiProtein Corp., Seongnam-si 13493, Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Korea.
Int J Mol Sci. 2021 Jun 10;22(12):6268. doi: 10.3390/ijms22126268.
To increase the half-life of growth hormones, we proposed its long-lasting regulation through the ubiquitin-proteasome system (UPS). We identified lysine residues (K67, K141, and K166) that are involved in the ubiquitination of human growth hormone (hGH) using ubiquitination site prediction programs to validate the ubiquitination sites, and then substituted these lysine residues with arginine residues. We identified the most effective substituent (K141R) to prevent ubiquitination and named it AUT-hGH. hGH was expressed and purified in the form of hGH-His, and ubiquitination was first verified at sites containing K141 in the blood stream. Through the study, we propose that AUT-hGH with an increased half-life could be used as a long-lasting hGH in the blood stream.
为了延长生长激素的半衰期,我们提出通过泛素-蛋白酶体系统(UPS)对其进行长效调节。我们使用泛素化位点预测程序识别了参与人生长激素(hGH)泛素化的赖氨酸残基(K67、K141 和 K166),以验证泛素化位点,然后将这些赖氨酸残基突变为精氨酸残基。我们确定了最有效的取代物(K141R)来阻止泛素化,并将其命名为 AUT-hGH。hGH 以 hGH-His 的形式表达和纯化,并首先在血液中含有 K141 的位点验证了泛素化。通过这项研究,我们提出具有延长半衰期的 AUT-hGH 可以作为血液中长效的 hGH 使用。