Matches in SemOpenAlex for { <https://semopenalex.org/work/W2889824417> ?p ?o ?g. }
- W2889824417 endingPage "30" @default.
- W2889824417 startingPage "16" @default.
- W2889824417 abstract "Abstract Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in the autosomal dominant polycystic kidney disease, regulates a number of processes including bone development. Activity of the transcription factor RunX2, which controls osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism governing PC1 activation of RunX2 is unclear. PC1 undergoes regulated cleavage that releases its C-terminal tail (CTT), which translocates to the nucleus to modulate transcriptional pathways involved in proliferation and apoptosis. We find that the cleaved CTT of PC1 (PC1-CTT) stimulates the transcriptional coactivator TAZ (Wwtr1), an essential coactivator of RunX2. PC1-CTT physically interacts with TAZ, stimulating RunX2 transcriptional activity in pre-osteoblast cells in a TAZ-dependent manner. The PC1-CTT increases the interaction between TAZ and RunX2 and enhances the recruitment of the p300 transcriptional co-regulatory protein to the TAZ/RunX2/PC1-CTT complex. Zebrafish injected with morpholinos directed against pkd1 manifest severe bone calcification defects and a curly tail phenotype. Injection of messenger RNA (mRNA) encoding the PC1-CTT into pkd1-morphant fish restores bone mineralization and reduces the severity of the curly tail phenotype. These effects are abolished by co-injection of morpholinos directed against TAZ. Injection of mRNA encoding a dominant-active TAZ construct is sufficient to rescue both the curly tail phenotype and the skeletal defects observed in pkd1-morpholino treated fish. Thus, TAZ constitutes a key mechanistic link through which PC1 mediates its physiological functions." @default.
- W2889824417 created "2018-09-27" @default.
- W2889824417 creator A5023948010 @default.
- W2889824417 creator A5029609763 @default.
- W2889824417 creator A5035012559 @default.
- W2889824417 creator A5035829700 @default.
- W2889824417 creator A5041557565 @default.
- W2889824417 creator A5065846162 @default.
- W2889824417 creator A5073475556 @default.
- W2889824417 creator A5080095018 @default.
- W2889824417 date "2018-09-12" @default.
- W2889824417 modified "2023-10-12" @default.
- W2889824417 title "Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ" @default.
- W2889824417 cites W1966685035 @default.
- W2889824417 cites W1967872597 @default.
- W2889824417 cites W1969887954 @default.
- W2889824417 cites W1978228345 @default.
- W2889824417 cites W1981137206 @default.
- W2889824417 cites W1981982858 @default.
- W2889824417 cites W1985268553 @default.
- W2889824417 cites W1987007903 @default.
- W2889824417 cites W1992077718 @default.
- W2889824417 cites W1994596418 @default.
- W2889824417 cites W1995071144 @default.
- W2889824417 cites W1996655557 @default.
- W2889824417 cites W1997812904 @default.
- W2889824417 cites W2001536138 @default.
- W2889824417 cites W2003535733 @default.
- W2889824417 cites W2005026678 @default.
- W2889824417 cites W2010237592 @default.
- W2889824417 cites W2012867369 @default.
- W2889824417 cites W2014264816 @default.
- W2889824417 cites W2014604277 @default.
- W2889824417 cites W2022281569 @default.
- W2889824417 cites W2025046506 @default.
- W2889824417 cites W2025545218 @default.
- W2889824417 cites W2030433725 @default.
- W2889824417 cites W2034042492 @default.
- W2889824417 cites W2036588212 @default.
- W2889824417 cites W2040190828 @default.
- W2889824417 cites W2044144053 @default.
- W2889824417 cites W2047052174 @default.
- W2889824417 cites W2048209974 @default.
- W2889824417 cites W2050853343 @default.
- W2889824417 cites W2053062434 @default.
- W2889824417 cites W2055689209 @default.
- W2889824417 cites W2058517860 @default.
- W2889824417 cites W2063191450 @default.
- W2889824417 cites W2067954113 @default.
- W2889824417 cites W2068642486 @default.
- W2889824417 cites W2073157874 @default.
- W2889824417 cites W2080727476 @default.
- W2889824417 cites W2082625064 @default.
- W2889824417 cites W2083547191 @default.
- W2889824417 cites W2086332492 @default.
- W2889824417 cites W2090905561 @default.
- W2889824417 cites W2091054780 @default.
- W2889824417 cites W2095869636 @default.
- W2889824417 cites W2097214606 @default.
- W2889824417 cites W2099007621 @default.
- W2889824417 cites W2100143771 @default.
- W2889824417 cites W2103377139 @default.
- W2889824417 cites W2107211482 @default.
- W2889824417 cites W2116517031 @default.
- W2889824417 cites W2118867845 @default.
- W2889824417 cites W2119367007 @default.
- W2889824417 cites W2121190335 @default.
- W2889824417 cites W2123511906 @default.
- W2889824417 cites W2124196467 @default.
- W2889824417 cites W2126712555 @default.
- W2889824417 cites W2130671879 @default.
- W2889824417 cites W2135389531 @default.
- W2889824417 cites W2136875701 @default.
- W2889824417 cites W2138714101 @default.
- W2889824417 cites W2141313696 @default.
- W2889824417 cites W2142227033 @default.
- W2889824417 cites W2152299918 @default.
- W2889824417 cites W2153038369 @default.
- W2889824417 cites W2153066126 @default.
- W2889824417 cites W2153155610 @default.
- W2889824417 cites W2153847689 @default.
- W2889824417 cites W2154435852 @default.
- W2889824417 cites W2154643490 @default.
- W2889824417 cites W2159196011 @default.
- W2889824417 cites W2159310898 @default.
- W2889824417 cites W2160674488 @default.
- W2889824417 cites W2161998042 @default.
- W2889824417 cites W2164020057 @default.
- W2889824417 cites W2170651583 @default.
- W2889824417 cites W2171561617 @default.
- W2889824417 cites W2541977924 @default.
- W2889824417 cites W2552102609 @default.
- W2889824417 cites W2768474602 @default.
- W2889824417 doi "https://doi.org/10.1093/hmg/ddy322" @default.
- W2889824417 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6298236" @default.
- W2889824417 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30215740" @default.
- W2889824417 hasPublicationYear "2018" @default.
- W2889824417 type Work @default.