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

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.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Wang Y,Li Y,Hu G,Huang X,Rao H,Xiong X,Luo Z,Lu Q,Luo S

doi

10.1016/j.cellsig.2016.06.010

subject

Has Abstract

pub_date

2016-09-01 00:00:00

pages

1304-13

issue

9

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(16)30144-9

journal_volume

28

pub_type

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