Ci protein, short for Cubitus interruptus, is a zinc finger containing transcription factor[1] involved in the Hedgehog signaling pathway.[2] In the absence of a signal to the Hedgehog signaling pathway, the Ci protein is cleaved and destroyed in proteasomes. It isn't, however, completely destroyed; part of the protein survives and acts as a repressor in the nucleus, keeping genes responsive to the Hedgehog signal silent.
Degradation of Ci
The degradation of Ci protein depends on a large multiprotein complex, which contains a serine/threonine kinase of unknown function, an anchoring protein that binds to microtubules (to keep the Ci protein out of the nucleus) and an adaptor protein.[3] When the Hedgehog signaling pathway is turned on, the Ci proteolysis is suppressed and the unprocessed CI protein enters the nucleus, where it activates the transcription of its target genes. Ci undergoes complete or partial degradation in the cells, the detailed molecular mechanism is poorly understood. It has been reported that an AAA ATPase Ter94 complex and K11/K48 ubiquitin chains are involved in the selection of Ci degradation.[4]
Target genes
- The Wingless protein in Drosophila, which is crucial to the embryogenesis of the fruit fly, and acts through the Wnt signaling pathway.
- The Patched receptor protein of the Hedgehog signaling pathway, which production acts as a negative feedback, since the resulting increase in Patched protein on the cell surface inhibits the Hedgehog pathway.[5]
References
- ^ Von Ohlen T, Lessing D, Nusse R, Hooper JE (March 1997). "Hedgehog signaling regulates transcription through cubitus interruptus, a sequence-specific DNA binding protein". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2404–9. Bibcode:1997PNAS...94.2404V. doi:10.1073/pnas.94.6.2404. PMC 20100. PMID 9122207.
- ^ Cohen MM (November 2003). "The hedgehog signaling network". Am. J. Med. Genet. A. 123 (1): 5–28. doi:10.1002/ajmg.a.20495. PMID 14556242. S2CID 31906029.
- ^ Jiang J (September 2002). "Degrading Ci: who is Cul-pable?". Genes Dev. 16 (18): 2315–21. doi:10.1101/gad.1027902. PMID 12231619.
- ^ Zhang, Zhao; Lv, Xiangdong; Yin, Wen-chi; Zhang, Xiaoyun; Feng, Jing; Wu, Wenqing; Hui, Chi-chung; Zhang, Lei; Zhao, Yun (2013-06-24). "Ter94 ATPase complex targets k11-linked ubiquitinated ci to proteasomes for partial degradation". Developmental Cell. 25 (6): 636–644. doi:10.1016/j.devcel.2013.05.006. ISSN 1878-1551. PMID 23747190.
- ^ Hepker J, Wang QT, Motzny CK, Holmgren R, Orenic TV (January 1997). "Drosophila cubitus interruptus forms a negative feedback loop with patched and regulates expression of Hedgehog target genes". Development. 124 (2): 549–58. PMID 9053330.
External links
- ci+protein,+Drosophila at the US National Library of Medicine Medical Subject Headings (MeSH)
- Drosophila cubitus interruptus - The Interactive Fly