USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling

USP15 targets ALK3/BMPR1A for deubiquitylation to enhance bone morphogenetic protein signalling

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Protein kinase ALK3/BMPR1A mediates bone morphogenetic protein (BMP) signalling g35 coupe fender through phosphorylation and activation of SMADs 1/5/8.SMAD6, a transcriptional target of BMP, negatively regulates the BMP pathway by recruiting E3 ubiquitin ligases and targeting ALK3 for ubiquitin-mediated degradation.Here, we identify a deubiquitylating enzyme USP15 as an interactor of SMAD6 and ALK3.We show that USP15 enhances BMP-induced phosphorylation of SMAD1 by interacting with and deubiquitylating ALK3.RNAi-mediated depletion of USP15 increases ALK3 K48-linked polyubiquitylation, and reduces both BMP-induced SMAD1 phosphorylation and transcription of BMP target genes.

We also natio glide on eyeshadow stick show that loss of USP15 expression from mouse myoblast cells inhibits BMP-induced osteoblast differentiation.Furthermore, USP15 modulates BMP-induced phosphorylation of SMAD1 and transcription during Xenopus embryogenesis.