title: Nek1 and TAZ interact to maintain normal levels of polycystin 2.
abstract: Polycystic kidney disease (PKD) in mice can arise from defects in Nek kinases, which participate in ciliogenesis. PKD can also arise from loss of the protein TAZ, an adaptor protein in the E3 ubiquitin ligase complex that targets the ciliary protein polycystin 2 (PC2) for degradation, but whether Nek and TAZ contribute to the same biochemical pathway is unknown. Here, we report that the nimA-related protein kinase Nek1 phosphorylates TAZ at a site essential for the ubiquitination and proteasomal degradation of PC2. Loss of Nek1 leads to underphosphorylation of TAZ, thereby promoting the abnormal accumulation of PC2. Furthermore, TAZ targets Nek1 for degradation. These data suggest that TAZ and Nek1 constitute a negative feedback loop linked through phosphorylation and ubiquitination and that the interaction of Nek1 and TAZ maintain PC2 at the level needed for proper ciliogenesis.
authors.affiliation: Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, NRB-0939, Boston, MA 02115, USA.
authors.forename: Hyungshin
authors.initials: H
authors.lastname: Yim
authors.forename: Chang K
authors.initials: CK
authors.lastname: Sung
authors.forename: John
authors.initials: J
authors.lastname: You
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
mesh_terms: D000217:Acyltransferases; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002923:Cilia / Q000502:physiology; D051379:Mice; D000072380:NIMA-Related Kinase 1; D010766:Phosphorylation; D007690:Polycystic Kidney Diseases / Q000209:etiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D050396:TRPP Cation Channels / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D000217:Acyltransferases; D018797:Cell Cycle Proteins; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases; D050396:TRPP Cation Channels; D014157:Transcription Factors; C486363:tafazzin protein, mouse; C000606920:Nek1 protein, mouse