Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950344956> ?p ?o ?g. }
- W2950344956 endingPage "190" @default.
- W2950344956 startingPage "180" @default.
- W2950344956 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 posttranslational processing and degradation of BMP2 in situ, linked to its secretion, have not been understood. Toward 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 substitutions on four lysine residues within the pro-BMP2 region and three in the mature region increased both BMP2 stability and extracellular secretion. Structural modeling revealed key lysine residues involved in proteasomal degradation occupy a lysine cluster near proprotein convertase cleavage site. Interestingly, mutations within these residues did not affect biological activity of BMP2. These data suggest that preventing intracellular proteasomal loss of BMP2 through genetic modifications can overcome limitations related to its short half-life." @default.
- W2950344956 created "2019-06-27" @default.
- W2950344956 creator A5003832488 @default.
- W2950344956 creator A5017420879 @default.
- W2950344956 creator A5022475656 @default.
- W2950344956 creator A5045141172 @default.
- W2950344956 creator A5070310048 @default.
- W2950344956 date "2019-01-02" @default.
- W2950344956 modified "2023-10-10" @default.
- W2950344956 title "Structural determinants and genetic modifications enhance BMP2 stability and extracellular secretion" @default.
- W2950344956 cites W101331579 @default.
- W2950344956 cites W1520151781 @default.
- W2950344956 cites W1904729061 @default.
- W2950344956 cites W1967321389 @default.
- W2950344956 cites W1980754871 @default.
- W2950344956 cites W1981701289 @default.
- W2950344956 cites W1986960611 @default.
- W2950344956 cites W1998727589 @default.
- W2950344956 cites W2008943389 @default.
- W2950344956 cites W2012886552 @default.
- W2950344956 cites W2028396860 @default.
- W2950344956 cites W2047647310 @default.
- W2950344956 cites W2049401592 @default.
- W2950344956 cites W2057347158 @default.
- W2950344956 cites W2060206278 @default.
- W2950344956 cites W2060561853 @default.
- W2950344956 cites W2064639714 @default.
- W2950344956 cites W2065697878 @default.
- W2950344956 cites W2075927574 @default.
- W2950344956 cites W2075951292 @default.
- W2950344956 cites W2076049057 @default.
- W2950344956 cites W2082354759 @default.
- W2950344956 cites W2093400854 @default.
- W2950344956 cites W2094529646 @default.
- W2950344956 cites W2097878023 @default.
- W2950344956 cites W2102773476 @default.
- W2950344956 cites W2108595411 @default.
- W2950344956 cites W2108957823 @default.
- W2950344956 cites W2110149781 @default.
- W2950344956 cites W2120833265 @default.
- W2950344956 cites W2121685422 @default.
- W2950344956 cites W2136681370 @default.
- W2950344956 cites W2147451371 @default.
- W2950344956 cites W2150271494 @default.
- W2950344956 cites W2155046952 @default.
- W2950344956 cites W2159831275 @default.
- W2950344956 cites W2188698563 @default.
- W2950344956 cites W2261324366 @default.
- W2950344956 cites W2343938601 @default.
- W2950344956 cites W2550452600 @default.
- W2950344956 cites W2598850272 @default.
- W2950344956 cites W2779360780 @default.
- W2950344956 cites W2804822363 @default.
- W2950344956 doi "https://doi.org/10.1096/fba.2018-00023" @default.
- W2950344956 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6586023" @default.
- W2950344956 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31225515" @default.
- W2950344956 hasPublicationYear "2019" @default.
- W2950344956 type Work @default.
- W2950344956 sameAs 2950344956 @default.
- W2950344956 citedByCount "9" @default.
- W2950344956 countsByYear W29503449562020 @default.
- W2950344956 countsByYear W29503449562021 @default.
- W2950344956 countsByYear W29503449562022 @default.
- W2950344956 countsByYear W29503449562023 @default.
- W2950344956 crossrefType "journal-article" @default.
- W2950344956 hasAuthorship W2950344956A5003832488 @default.
- W2950344956 hasAuthorship W2950344956A5017420879 @default.
- W2950344956 hasAuthorship W2950344956A5022475656 @default.
- W2950344956 hasAuthorship W2950344956A5045141172 @default.
- W2950344956 hasAuthorship W2950344956A5070310048 @default.
- W2950344956 hasBestOaLocation W29503449561 @default.
- W2950344956 hasConcept C104317684 @default.
- W2950344956 hasConcept C185592680 @default.
- W2950344956 hasConcept C202751555 @default.
- W2950344956 hasConcept C25602115 @default.
- W2950344956 hasConcept C2776016237 @default.
- W2950344956 hasConcept C28406088 @default.
- W2950344956 hasConcept C30352789 @default.
- W2950344956 hasConcept C49039625 @default.
- W2950344956 hasConcept C515207424 @default.
- W2950344956 hasConcept C55493867 @default.
- W2950344956 hasConcept C79879829 @default.
- W2950344956 hasConcept C86803240 @default.
- W2950344956 hasConcept C95444343 @default.
- W2950344956 hasConceptScore W2950344956C104317684 @default.
- W2950344956 hasConceptScore W2950344956C185592680 @default.
- W2950344956 hasConceptScore W2950344956C202751555 @default.
- W2950344956 hasConceptScore W2950344956C25602115 @default.
- W2950344956 hasConceptScore W2950344956C2776016237 @default.
- W2950344956 hasConceptScore W2950344956C28406088 @default.
- W2950344956 hasConceptScore W2950344956C30352789 @default.
- W2950344956 hasConceptScore W2950344956C49039625 @default.
- W2950344956 hasConceptScore W2950344956C515207424 @default.
- W2950344956 hasConceptScore W2950344956C55493867 @default.
- W2950344956 hasConceptScore W2950344956C79879829 @default.
- W2950344956 hasConceptScore W2950344956C86803240 @default.
- W2950344956 hasConceptScore W2950344956C95444343 @default.
- W2950344956 hasFunder F4320306078 @default.