Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ

Human Molecular Genetics
David MerrickMichael J Caplan

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 ...Continue Reading

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Citations

Nov 22, 2018·Journal of Cellular Biochemistry·Antonios N GargalionisAthanasios G Papavassiliou
May 6, 2019·International Journal of Molecular Sciences·Antonios N GargalionisAthanasios G Papavassiliou
Jun 28, 2020·Journal of Cellular and Molecular Medicine·Chiara FormicaUNKNOWN DIPAK Consortium
Nov 14, 2019·Scientific Reports·Elisa Agnese NigroAlessandra Boletta
Feb 23, 2021·American Journal of Physiology. Renal Physiology·Elisa A Nigro, Alessandra Boletta
Apr 20, 2020·Cellular Signalling·Robin L Maser, James P Calvet
Apr 14, 2020·Cellular Signalling·Valeria PadovanoMichael J Caplan
Mar 30, 2021·Clinical Kidney Journal·Steven Van Laecke, Wim Van Biesen

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