Xpo7 negatively regulates Hedgehog signaling by exporting Gli2 from the nucleus

Markiewicz, Łukasz; Uśpieński, Tomasz; Baran, Brygida; Niedziółka, Sylwia M.; Niewiadomski, Paweł

doi:10.1016/j.cellsig.2020.109907

Cited by 8 publications

(2 citation statements)

References 52 publications

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“…We identified 473 high confidence Gli3 interactors by rejecting frequent IP/MS contaminants based on the CRAPome database 30 . In this dataset, we found well-known Gli interaction partners, such as SuFu, Kif7, and Xpo7 [31][32][33][34] . The dataset was enriched for proteins involved in intraciliary and vesicle transport, chromatin remodeling, and DNA repair (Fig.…”

Section: The Exocyst Complex Interacts With Gli3mentioning

confidence: 87%

The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium

Niedziółka

Datta

Uśpieński

et al. 2021

Preprint

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Efficient transport of proteins into the primary cilium is a crucial step for many signaling pathways. Dysfunction of this process can lead to the disruption of signaling cascades or cilium assembly, resulting in developmental disorders and cancer. Previous studies on ciliary trafficking were mostly focused on the membrane-embedded receptors. In contrast, how soluble proteins are delivered into the cilium is poorly understood. In our work, we identify the exocyst complex as a key player in the ciliary trafficking of soluble Gli transcription factors. Considering that the exocyst mediates intracellular vesicle transport, we demonstrate that soluble proteins, including Gli2/3 and Lkb1, can use the endosome recycling machinery for their delivery to the primary cilium. Finally, we identify GTPases: Rab14, Rab18, Rab23, and Arf4 involved in vesicle-mediated Gli protein ciliary trafficking. Our data pave the way for a better understanding of ciliary transport and uncover novel transport mechanisms inside the cell.

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Section: The Exocyst Complex Interacts With Gli3mentioning

confidence: 87%

The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium

Niedziółka

Datta

Uśpieński

et al. 2021

Preprint

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“…[57] However, the effects of GLI repression in this assay are magnified by the nuclear localization of GLI-R compared to GLI activator, which has nuclear export signals. [58,59] Most significantly, these experiments were done with standard plasmids that do not incorporate histones, findings that need to be re-evaluated since GLI repression occurs at least in part through regulating histone acetylation at enhancers.…”

Section: Conclusion: Gli Repression Is Not a Default State For The He...mentioning

confidence: 99%

Timing is everything: Transcriptional repression is not the default mode for regulating Hedgehog signaling

Lex

Vokes

2022

BioEssays

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Hedgehog (HH) signaling is a conserved pathway that drives developmental growth and is essential for the formation of most organs. The expression of HH target genes is regulated by a dual switch mechanism where GLI proteins function as bifunctional transcriptional activators (in the presence of HH signaling) and transcriptional repressors (in the absence of HH signaling). This results in a tight control of GLI target gene expression during rapidly changing levels of pathway activity. It has long been presumed that GLI proteins also repress target genes prior to the initial expression of HH in a given tissue. This idea forms the basis for the limb bud pre-patterning model for regulating digit number. Recent findings indicate that GLI repressor proteins are indeed present prior to HH signaling but contrary to this model, GLI proteins are inert as they do not regulate transcriptional responses or enhancer chromatin modifications at this time.These findings suggest that GLI transcriptional repressor activity is not a default state as assumed, but is itself regulated in an unknown fashion. We discuss these findings and their implications for understanding pre-patterning, digit regulation, and HH-driven disease.

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