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A tumour suppressor in mice and men

Reinhard Fässler led a team which has published an article on this topic in the latest edition of Cell. A protein called Cyld controls Bcl-3 - and thus protects mice from tumour growth. The researchers were able to describe the cellular signalling path which causes uncontrolled growth when the Cyld gene is defective. Furthermore, there is evidence that such a defective Cyld gene may be the root cause of kidney, liver, uterus, and large intestine tumours. Cyld could possibly be one of Bcl-3's most important opponents - in mice and men (Cell, May 19 2006).

Growth, separation, and differentiation of cells is one of the body's most well regulated processes. Even just a single cell escaping this regulation can lead to a tumour. Oncogenes are, in this sense, like ticking time bombs, which can cause cancer. Their activity is controlled in healthy cells by tumour suppressor genes. The cellular "opponents" of the Bcl-3 oncogene, however, had not yet been known before this study. The protein has to find its way to the nucleus to function as what is called a "transcription factor". These initiate and support genetic transcription - DNA fragments codified by proteins. This process is necessary for transcribing genetic information during protein synthesis.

During the process of genetic transcription, Bcl-3 cooperates with other, unusually important transcription factors which belong to the NF-κB-family. Its five members influence a broad spectrum of disease processes, like infections and immune reactions, as well as cell growth. Two representatives of this group, p50 and p52, must themselves first be activated in order to initiate the transcription. One important mechanism for doing that is Bcl-3 binding. Until now, we have known that Bcl-3 can cooperate with p50 or p52, causing intense cell growth and ultimately cancer. For such cooperation, however, Bcl-3 has to first enter the nucleus, where DNA and the NF-κB proteins can be found. The team from Munich, led by
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Contact: Eva-Maria Diehl
diehl@biochem.mpg.de
49-898-578-2824
Max-Planck-Gesellschaft
29-May-2006


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