Abstract
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.
Highlights
(K166R) mutants as compared to the wild-type (WT) (Figure 1B, lanes 3–5). These results suggest that a smaller amount of ubiquitin was detected because the ubiquitin did not bind to the mutant human growth hormone (hGH)
These results indicate that ubiquitin first binds to an hGH, and a poly ubiquitin chain is formed, and the hGH is degraded by the ubiquitin-proteasome system (UPS)
Neutropin Depot was withdrawn from the market because it was less effective than the first generation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Various protein fusion techniques including PEGylation (where PEG stands for polyethylene glycol), binding with albumin or antigen-binding fragment (Fab), and fusion with other proteins, have recently been attempted to develop sustained growth hormones [13]. Representative products using these techniques are GX-H9 [14,15], MOD4023 [16,17] LAPSrhGH [13] AG-B1512 [13], Somapacitan [18,19,20], Jintrolong [21,22], and so on. This suggests that AUT-hGH with an increased half-life might be a long-lasting hGH in the blood stream
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
