Lehrstuhl für Experimentelle Medizin II
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  Conductin in the Cell Cycle and Chromosomal Instability
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Tumour Suppressor APC

Amer Family of Proteins

Conductin in Cancer

Activin B and renal cell carcinoma


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Functional characterization of Conductin in cancer

Conductin, also known as Axin2, is a scaffold protein that together with the related Axin1 promotes scaffolding of b-catenin in the so-called „destruction complex“, thereby negatively regulating Wnt signalling. Conductin is at the same time a target gene of the Wnt signalling, implicated in a negative feedback loop. We have recently discovered that conductin can localize to centrosomes and the mitotic spindle and that it regulates the spindle checkpoint, which oversees accurate segregation of chromosomes during mitosis. Mistakes during this time due to a faulty checkpoint accounts for chromosome mis-segregation and can give rise to aneuploidy and chromosomal instability (CIN), two hallmarks of colon cancer. Conductin, which is highly expressed selectively in CIN positive colon cancers as a result of aberrant Wnt signalling, can suppress the spindle checkpoint and can lead to CIN. This could account for the CIN observed in these tumours and suggests that aberrant Wnt signalling, an early event in carcinogenesis, could potentially promote cancer by inducing CIN. We are currently investigating the influence of high conductin expression on CIN and tumourigenesis through transgenic mouse technology. In addition, we are analysing the specific function(s) of conductin at mitotic spindles, centrosomes and during cell cycle progression. Our recent data suggest that conductin also plays a role in centrosome cohesion and cell cycle progression.