Axin
| Axin-1 | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 862 amino acids | |
| Secondary to quaternary structure | Homodimer | |
| Isoforms | 2 | |
| Identifier | ||
| Gene name | AXIN1 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | multicellular animals | |
| Axin-2 | ||
|---|---|---|
| Properties of human protein | ||
| Mass / length primary structure | 843 amino acids | |
| Identifier | ||
| Gene name | AXIN2 | |
| External IDs | ||
| Occurrence | ||
| Parent taxon | multicellular animals | |
Axin (from English: axis inhibition protein ) are two paralogous proteins in animals that are essential for the correct development of the embryo . In the adult animal they are involved in the regulation of the Wnt signaling pathway and Axin-1 acts as a tumor suppressor . While Axin-1 is expressed in all cell types, only the human brain and lymphoblasts produce Axin-2. Mutations in AXIN1 - gene can hepatocellular carcinoma lead.
Axin in the WNT signaling pathway
In normal cells, Axin 1 and 2 form a complex ( destruction complex ) with APC and GSK-3 β , CK1α and β-catenin , whereby β-catenin is ubiquitinated by β-TRCP and can thus be broken down by the so-called proteasome . This complex is formed due to a dimerization of the membrane receptors Frizzled and LPR by the extracellular factor WNT . Due to the breakdown of β-catenin, its concentration in the cytosol remains low, which means that the gene expression of certain genes in the cell nucleus is blocked. In the case of a mutation of an axin gene, however, the destruction complex cannot be formed, which leads to a blockage of the β-catenin degradation, whereby the intracellular concentration of β-catenin increases. In the cell nucleus, β-catenin then binds to the protein complex TCF / LEF , which triggers the expression of many target genes, including c-Myc and cyclin D1 . The two proteins c-Myc and cyclin D1 are important proto-oncogenes and are thus involved in the development of a number of tumors. By mutating one or both axin genes, a cascade of processes is triggered that can lead to an increased rate of proliferation and thus to cancer.
Axin in the TGF-β signaling pathway
In the TGF-β signaling pathway, Axin activates the phosphorylation of SMAD3 , which triggers a cascade of processes. Together with other proteins, SMAD3 acts as a transcription factor , which ultimately leads to a stop of the cell cycle and apoptosis .
Axin in the SAPK / stress pathway
In the SAPK / stress signaling pathway , Axin activates the kinase MEKK1 , which in turn phosphorylates SAPK , which ultimately leads to apoptosis of the cell.
further reading
- Molecular Oncology (2009) Christoph Wagener, Oliver Müller; Georg Thieme Publishing House
Individual evidence
- ↑ a b homologues at inParanoid
- ↑ UniProt O15269
- ↑ Shi Y, Massagué J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus . (PDF) In: Cell . 113, No. 6, June 2003, pp. 685-700. PMID 12809600 .
- ↑ Masao Furuhashi, Ken Yagi, Hideki Yamamoto, Yoichi Furukawa, Shinji Shimada, Yusuke Nakamura, Akira Kikuchi, Kohei Miyazono, Mitsuyasu Kato (2001): Axin Facilitates Smad3 Activation in the Transforming Growth Factor β Signaling Pathway . In: Molecular and Cellular Biology , p. 5132-5141, vol. 21, no. 15th
Web links
- Kimelman / reactome: Degradation of beta-catenin by the destruction complex