negative regulation of hh target transcription factor activity

Definition

Target type: biologicalprocess

Any process that decreases the activity of a transcription factor that activates transcription of Hedgehog-target genes in response to Smoothened signaling. In Drosophila, Cubitus interruptus (Ci) is the only identified transcription factor so far in the Hedgehog signaling pathway. In vertebrates members of the Gli protein family are activated by Hedgehog signaling. [GOC:bhm, PMID:24311597]

Negative regulation of Hedgehog (Hh) target transcription factor activity is a crucial biological process that ensures proper development and tissue patterning. The Hh signaling pathway is highly conserved and plays a critical role in a variety of developmental processes, including embryonic development, cell proliferation, and tissue regeneration. The Hh pathway involves a complex series of molecular interactions, starting with the binding of Hh ligands to the Patched (Ptch) receptor, which in turn inhibits the activity of the Smoothened (Smo) receptor. This inhibition is relieved upon Hh ligand binding, allowing Smo to activate a downstream signaling cascade that leads to the transcription of target genes.

One of the key components of this pathway is the transcription factor Cubitus interruptus (Ci) in Drosophila or Gli in mammals. In the absence of Hh signaling, Ci is proteolytically processed into a repressor form (CiR) that binds to the promoters of target genes and represses their transcription. Conversely, in the presence of Hh signaling, Smo activates a signaling cascade that prevents the proteolytic processing of Ci, leading to the accumulation of the full-length activator form (CiA). CiA then translocates to the nucleus, where it binds to the promoters of target genes and activates their transcription.

Negative regulation of Hh target transcription factor activity is essential for maintaining proper developmental processes. This regulation is achieved through a variety of mechanisms, including:

* **Proteolytic processing of Ci/Gli:** This process results in the production of a repressor form that prevents the activation of Hh target genes.
* **Direct inhibition of Ci/Gli activity:** Various proteins, including Suppressor of fused (Sufu) and kinesin-like protein (Kif7), directly bind to Ci/Gli and inhibit their activity.
* **Regulation of Ci/Gli transcription:** The expression levels of Ci/Gli are tightly regulated, ensuring that the appropriate levels of activator and repressor forms are present at specific developmental stages.
* **Regulation of Hh ligand production and signaling:** The activity of the Hh pathway is regulated by feedback loops that control the production and signaling of Hh ligands, ensuring proper spatiotemporal control of Hh target gene expression.

The negative regulation of Hh target transcription factor activity is essential for preventing uncontrolled growth, differentiation, and patterning defects. Aberrant regulation of this process has been implicated in various developmental disorders and cancers. Understanding the molecular mechanisms underlying the negative regulation of Hh target transcription factor activity is crucial for developing new therapeutic strategies for these diseases.'
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Proteins (1)

Compounds (8)