Ribosome Malfunction May Cause Cancer

A study has found that the rare genetic syndrome dyskeratosis congenita (DC) is caused by ribosome malfunction and not by telomere shortening as had been previously thought. The study appeared in the January 10, 2003, issue of Science.

Dyskeratosis congenita is an extremely rare, fatal X-linked recessive disease that results in premature aging, severe anemia due to bone marrow failure, dyskeratosis of the nails, skin hyperpigmentation, and cancer. It is caused by mutations in the DKC1 gene that encodes the protein dyskerin.

In order to study DC, investigators from the Memorial Sloan-Kettering Cancer Center (New York, NY, USA; www.mskcc.org) genetically engineered a line of DKC1 mutant mice that accurately expressed the phenotypes found in DC. All the major features of DC, including premature aging, dyskeratosis of the skin, bone marrow failure, and susceptibility to tumor development, showed up in the first and second-generation mice. However, overt defects in telomere length were only evident beginning with the fourth or fifth generations. This showed that the primary cause of DC was not telomerase impairment but rather deregulated ribosome function.

"This is the first example that shows that a defect in ribosome function may cause cancer,” explained first author Dr. Davide Ruggero, of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering. "In the past, we thought of ribosome as an important but passive ‘machine' in the synthesis of proteins while our study suggests that it plays a more active role in maintaining proper cellular function.”

The authors concluded that ribosome malfunction might be important in the genesis of cancer and might have clinical implications for the identification of new molecular targets for cancer drugs.



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Memorial Sloan-Kettering Cancer Center