GLI-SUFU complex

Definition

Target type: cellularcomponent

A protein repressing GLI's transcription factor activity when SMO signaling is inactive. Upon ligand binding to the upstream receptor PTC (Patched) GLI dissociates from SUFU and activates transcription of hedgehog-target genes. In mammals it consists of SUFU and one of the GLI family proteins. [GOC:bhm, PMID:24311597]

The GLI-SUFU complex is a key regulatory element in the Hedgehog (Hh) signaling pathway, which plays a crucial role in embryonic development and tissue homeostasis. The complex consists of two main components: GLI transcription factors and Suppressor of Fused (SUFU).

GLI proteins are zinc finger transcription factors that act as downstream effectors of the Hh pathway. They can either activate or repress gene expression depending on their specific isoforms and the context of the signaling pathway. There are three main GLI proteins in mammals: GLI1, GLI2, and GLI3. GLI1 primarily acts as an activator, while GLI2 and GLI3 can act as both activators and repressors.

SUFU is a negative regulator of GLI activity. It binds to GLI proteins and sequesters them in the cytoplasm, preventing their translocation to the nucleus and their ability to regulate gene expression. SUFU also inhibits the activity of GLI proteins by promoting their phosphorylation and degradation.

The cellular localization of the GLI-SUFU complex is dynamic and depends on the presence or absence of Hh signaling. In the absence of Hh signaling, SUFU binds to GLI proteins and retains them in the cytoplasm. This interaction prevents GLI proteins from entering the nucleus and activating target genes. However, upon Hh ligand binding to its receptor Patched (Ptch), the signal transduction cascade is initiated, leading to the activation of Smoothened (Smo) and the subsequent release of GLI proteins from SUFU.

Once released from SUFU, GLI proteins translocate to the nucleus, where they bind to specific DNA sequences and regulate the transcription of target genes. The specific targets of GLI proteins vary depending on the specific GLI isoform and the cellular context. However, they are generally involved in the regulation of cell proliferation, differentiation, and survival.

The interaction between GLI and SUFU is a dynamic and regulated process, with multiple factors influencing the formation and stability of the GLI-SUFU complex. These factors include the availability of Hh ligand, the phosphorylation status of both GLI and SUFU, and the presence of other regulatory proteins.

In summary, the GLI-SUFU complex is a key regulatory element in the Hh signaling pathway, controlling the activity of GLI transcription factors. The cellular localization of the complex is dynamic and regulated by the presence or absence of Hh signaling, with implications for the expression of Hh target genes and the regulation of developmental processes.'
"

Proteins (2)

Compounds (8)