Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion.

ABSTRACT: The short half-life and use of recombinant bone morphogenetic protein (BMP)-2 in large doses poses major limitations in the clinic. Events regulating post-translational processing and degradation of BMP2 in situ, linked to its secretion, have not been understood. Towards identifying mechanisms regulating intracellular BMP2 stability, we first discovered that inhibiting proteasomal degradation enhances both intracellular BMP2 level and its extracellular secretion. Next, we identified BMP2 degradation occurs through an ubiquitin-mediated mechanism. Since ubiquitination precedes proteasomal turnover and mainly occurs on lysine residues of nascent proteins, we systematically mutated individual lysine residues within BMP2 and tested them for enhanced stability. Results revealed that subs

SUBMITTER: Khattar V 

PROVIDER: S-EPMC6586023 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature