KIF7 x GLI1

Last update 08 May 2025

Basic Info

Related Targets

KIF7GLI1

100 Clinical Results associated with KIF7 x GLI1

100 Translational Medicine associated with KIF7 x GLI1

0 Patents (Medical) associated with KIF7 x GLI1

Literatures (Medical) associated with KIF7 x GLI1

14 Mar 2025·Science Advances

Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking

Article

Author: Chadha, Abhishek ; Ku, Pei-I ; Williams, David S. ; Engelke, Martin F. ; Sreeja, Jamuna S. ; Subramanian, Radhika

In vertebrate Hedgehog (Hh) signaling, the precise output of the final effectors, GLI (glioma-associated oncogene) transcription factors, depends on the primary cilium. Upon pathway initiation, generating the precise levels of the activator form of GLI depends on its concentration at the cilium tip. The mechanisms underlying this critical step in Hh signaling are unclear. We developed an assay to visualize GLI2, the primary GLI activator isoform, at single-particle resolution within the cilium. We found that GLI2 is a cargo of intraflagellar transport (IFT) machinery. Anterograde-biased IFT loading of GLI2 in a restricted time window following pathway activation results in the tip accumulation of GLI2. Unexpectedly, we found that the conserved Hh regulator KIF7, a nonmotile kinesin, is important for the temporal control of IFT-mediated GLI2 transport and retention of GLI2 at the cilium tip. Our findings underscore a design principle where a cilia-specific cytoskeletal transport system and an Hh pathway–specific cytoskeletal protein collaboratively regulate GLI2 trafficking for Hh signaling.

01 Aug 2024·Leukemia

P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression

Article

Author: Jiang, Wei ; Du, Guiping ; Zhu, Zewen ; Li, Quanfu ; Liu, Yiyang ; Tan, Minjia ; Dang, Yongjun ; Huang, Hai ; Hu, Junchi ; Zhang, Ling ; Ma, Dengke K ; Fan, Jianjun ; Wu, Jingxian ; Zhai, Linhui ; Wang, Ziruoyu ; Liu, Jun O

AbstractAberrations in the Hedgehog (Hh) signaling pathway are significantly prevailed in various cancers, including B-cell lymphoma. A critical facet of Hh signal transduction involves the dynamic regulation of the suppressor of fused homolog (SUFU)-glioma-associated oncogene homolog (GLI) complex within the kinesin family member 7 (KIF7)-supported ciliary tip compartment. However, the specific post-translational modifications of SUFU-GLI complex within this context have remained largely unexplored. Our study reveals a novel regulatory mechanism involving prolyl 4-hydroxylase 2 (P4HA2), which forms a complex with KIF7 and is essential for signal transduction of Hh pathway. We demonstrate that, upon Hh pathway activation, P4HA2 relocates alongside KIF7 to the ciliary tip. Here, it hydroxylates SUFU to inhibit its function, thus amplifying the Hh signaling. Moreover, the absence of P4HA2 significantly impedes B lymphoma progression. This effect can be attributed to the suppression of Hh signaling in stromal fibroblasts, resulting in decreased growth factors essential for malignant proliferation of B lymphoma cells. Our findings highlight the role of P4HA2-mediated hydroxylation in modulating Hh signaling and propose a novel stromal-targeted therapeutic strategy for B-cell lymphoma.

01 Jul 2022·Nature Cell Biology

A kinesin mimics DNA

Article

Author: Reiter, Jeremy F ; Kumar, Dhivya

Primary cilia transduce cues, including Hedgehog (Hh) signals, and possess doublet microtubules that interact with kinesin motors.The kinesin KIF7 is important for Hh signalling and binds to GLI transcription factors.Haque et al. reveal that, surprisingly, GLI proteins bind a DNA-like part of KIF7 to promote their accumulation at the ciliary tip.

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