Identification of a Novel Link between the Protein Kinase NDR1 and TGFβ Signaling in Epithelial Cells

DSpace/Manakin Repository

Identification of a Novel Link between the Protein Kinase NDR1 and TGFβ Signaling in Epithelial Cells

Citable link to this page

 

 
Title: Identification of a Novel Link between the Protein Kinase NDR1 and TGFβ Signaling in Epithelial Cells
Author: Pot, Isabelle; Patel, Shachi; Deng, Lili; Chandhoke, Amrita Singh; Zhang, Chi; Bonni, Azad; Bonni, Shirin

Note: Order does not necessarily reflect citation order of authors.

Citation: Pot, Isabelle, Shachi Patel, Lili Deng, Amrita Singh Chandhoke, Chi Zhang, Azad Bonni, and Shirin Bonni. 2013. “Identification of a Novel Link between the Protein Kinase NDR1 and TGFβ Signaling in Epithelial Cells.” PLoS ONE 8 (6): e67178. doi:10.1371/journal.pone.0067178. http://dx.doi.org/10.1371/journal.pone.0067178.
Full Text & Related Files:
Abstract: Transforming growth factor-beta (TGFβ) is a secreted polypeptide that plays essential roles in cellular development and homeostasis. Although mechanisms of TGFβ-induced responses have been characterized, our understanding of TGFβ signaling remains incomplete. Here, we uncover a novel function for the protein kinase NDR1 (nuclear Dbf2-related 1) in TGFβ responses. Using an immunopurification approach, we find that NDR1 associates with SnoN, a key component of TGFβ signaling. Knockdown of NDR1 by RNA interference promotes the ability of TGFβ to induce transcription and cell cycle arrest in NMuMG mammary epithelial cells. Conversely, expression of NDR1 represses TGFβ-induced transcription and inhibits the ability of TGFβ to induce cell cycle arrest in NMuMG cells. Mechanistically, we find that NDR1 acts in a kinase-dependent manner to suppress the ability of TGFβ to induce the phosphorylation and consequent nuclear accumulation of Smad2, which is critical for TGFβ-induced transcription and responses. Strikingly, we also find that TGFβ reciprocally regulates NDR1, whereby TGFβ triggers the degradation of NDR1 protein. Collectively, our findings define a novel and intimate link between the protein kinase NDR1 and TGFβ signaling. NDR1 suppresses TGFβ-induced transcription and cell cycle arrest, and counteracting NDR1's negative regulation, TGFβ signaling induces the downregulation of NDR1 protein. These findings advance our understanding of TGFβ signaling, with important implications in development and tumorigenesis.
Published Version: doi:10.1371/journal.pone.0067178
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694053/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11717563
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters