UbcD1 regulates the protein stability of Ci/Gli, the key transcription factor in the Hh signaling pathway.

The research by Zhao Yun, Institute of Biochemistry and Cell Biology, Shanghai Institute of Life Sciences, Chinese Academy of Sciences, is based on the ubcD1 regulates hedgehog signaling by directly modulating ci ubiquitination and processing, published online in EMBO Reports.
the study found that UbcD1 regulates the protein stability of Ci/Gli, the key transcription factor in the Hh signaling pathway.
Hh signaling pathways play an important role in embryonic development, solid tissue stability maintenance and tumor development. Abnormalities in the
Hh signaling pathways can cause a variety of serious human diseases, including some birth defects and cancers. The activity of the
transcription factor Ci/Gli is strictly regulated by a variety of post-translation modifications, in which the ubiquitic-mediated protease degradation directly regulates the stability and protein level of Ci/Gli, so it has an important regulatory effect on the activity level of the Hh signaling pathway.
there are two important ubiquitinization control methods in the Hh signal path.
selective partial degradation by Slimb-Cul1 E3 Ligase mediated Ci/Gli ubiquitiatiating when there is no Hh signal, and in the presence of a high concentration hh signal, full degradation occurs by Rdx-Cul3 E3 Ligase mediated Ci/Gli ubiquitization. Prior research by zhao Yun Research Group
found that in the ci/Gli selective degradation process, Ter94 ATPase complex, UB lysine K11 ubiquitin chain and Sqh molecules were very important for the selective partial degradation of the mediated Ci/Gli, while the ubiquity enzyme Usp7 participated in the stability regulation of Ci/Gli by regulating ubiquitin levels.
However, it is unknown whether the ubiquitin-conjugating Enzyme is specific in the selective degradation process of Ci/Gli and whether it plays a role in determining the ubiquitin chain type.
study, Dr. Pan Chenyu of Zhao Yun's research group found through genetic screening that E2-UbcD1 regulates Ci/Gligamong protein stability and specifically participates in the Slimb-Cul1 E3 Ligase-mediated Ciualphine degradation process, which does not work during the Ci-Gligase-mediated Ci-Gligase degradation process.
UbcD1 is also involved in the formation of K-11 ubiquitin chains during The Ubiquitin degradation of Ci/Gli.
at the same time, this regulatory mechanism is highly conservative in vertebrates.
this work further reveals the stable regulatory mechanism of The Hh Path transcription factor Ci/Gli, and also provides a potential drug target for Ci/Gli degradation regulation.
the research was supported by the biochemical and cell cell analysis technology platform, fruit fly resource and technology platform, zebrafish technology platform and molecular biology technology platform, and received funding from the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and Shanghai.
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