New Light on Cancer Susceptibility

Susceptibility to cancer and other human diseases can be increased by genetic defects affecting the control of protein synthesis within cells. Also, defective protein production can occur in cells even when the genes controlling those proteins are normal. Experts attributed the protein defects to a critical glitch in the protein assembly line of ribosomes. Ribosomes, the protein factories of cells, use RNA to translate the DNA blueprint into functional proteins. A particular study focused on understanding control of ribosome activity and how disruptions in RNA translation predispose people to cancer.

The study shows that a gene mutation, Dkc1, that affects ribosome function underlie a progressive disease called dyskeratosis congenita. This involves abnormal bone marrow leading to anemia, severe immune deficiency and infections; increased risk of various cancers, including lymphoma; and, starting as early as age 10, skin abnormalities, nails and mucous membranes that resemble premature aging syndromes. There is a decrease in production of certain proteins due to a specific defect in RNA translation that depends on a sequence called internal ribosome entry site (IRES). This particular sequence occurs in only some of the messenger RNAs that translate the DNA code into proteins. Gene p27, which normally works to suppress tumors, governs one of these proteins with decreased levels. This may explain the increased tumor susceptibility seen in patients with dyskeratosis congenita. Scientists are seeing to apply their knowledge of protein synthesis control to the discovery of therapeutic agents that target the translational machinery in cancer cells and human disease.