Nek2A phosphorylates and stabilizes SuFu: A new strategy of Gli2/Hedgehog signaling regulatory

Yao Wang, Yong Li, Guanghui Hu, Xuan Huang, Hai Rao, Xiangyang Xiong, Zhijun Luo, Quqin Lu, Shiwen Luo

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Suppressor of Fused (SuFu) plays a conservative role in the regulation of the Gli transcription factors within the Hedgehog (Hh) signaling pathway. Despite the central importance of SuFu in the Hh pathway, little is known about its regulation. Here, we performed a GAL4-based yeast two-hybrid screen using human SuFu as bait, and identified NIMA-related expressed kinase 2A (Nek2A) as a new SuFu-interacting protein, which was also confirmed by glutathione-S-transferase pull-down and co-immunoprecipitation assays. Intriguingly, Nek2A is found to stabilize SuFu at least partly depending on its kinase activity, thereby triggering phosphorylation of the SuFu protein. Moreover, the phosphorylated SuFu inhibits the nuclear localization and transcriptional activity of Gli2/Hh signaling. These findings reveal a new mechanism of mammalian SuFu regulation, and offers novel insights into Hh signaling regulation in development and human disease.

Original languageEnglish (US)
Pages (from-to)1304-1313
Number of pages10
JournalCellular Signalling
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • Hedgehog signaling pathway
  • NIMA-related expressed kinase 2A
  • Phosphorylation
  • Suppressor of fused
  • Transcription factor Gli2

ASJC Scopus subject areas

  • Cell Biology

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