| Autor: |
Patricia A. Umberger, Stacey K. Ogden |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cell and Developmental Biology, Vol 9 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2296-634X |
| DOI: |
10.3389/fcell.2021.710295 |
| Popis: |
The speckle-type POZ protein (SPOP) functions as a guardian of genome integrity and controls transcriptional regulation by functioning as a substrate adaptor for CUL3/RING-type E3 ubiquitin ligase complexes. SPOP-containing CUL3 complexes target a myriad of DNA-binding proteins involved in DNA repair and gene expression, and as such, are essential modulators of cellular homeostasis. GLI transcription factors are effectors of the Hedgehog (HH) pathway, a key driver of tissue morphogenesis and post-developmental homeostasis that is commonly corrupted in cancer. CUL3-SPOP activity regulates amplitude and duration of HH transcriptional responses by controlling stability of GLI family members. SPOP and GLI co-enrich in phase separated nuclear droplets that are thought to serve as hot spots for CUL3-mediated GLI ubiquitination and degradation. A similar framework exists in Drosophila, in which the Hedgehog-induced MATH (meprin and traf homology) and BTB (bric à brac, tramtrack, broad complex) domain containing protein (HIB) targets the GLI ortholog Cubitus interruptus (Ci) for Cul3-directed proteolysis. Despite this functional conservation, the molecular mechanisms by which HIB and SPOP contribute to Drosophila and vertebrate HH signaling differ. In this mini-review we highlight similarities between the two systems and discuss evolutionary divergence in GLI/Ci targeting that informs our understanding of how the GLI transcriptional code is controlled by SPOP and CUL3 in health and disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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