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September 1, 2006


Breast cancer gene product has role in translation

  add to kirtsy       

Filed under: Breast Cancer — Trisha @ 12:01 am

Mutations in the gene BRCA1 (breast cancer 1) are associated with a greater risk of developing breast, ovarian, prostate and colon cancers. These mutations are found in around 90% of people with both breast and ovarian cancer and in 40% of women with familial breast cancer although they are found in only 5% of all breast cancers.

It is believed that the normal role of the BRCA1 protein is to suppress tumors, although details of its role in this regard are not fully known. So far BRCA1 has been shown to be involved in many cell processes including homology-directed repair of DNA, cell cycle regulation, apoptosis, transcription and ubiquitination.

A new paper in JBC by Nicole Dalla Venezia’s group now shows that BRCA1 may also be involved in translation. Translation is the process in which a mRNA (messenger RNA) is decoded and a protein is synthesized.

Venezia’s group first showed that BRCA1 binds to PABP (poly(A)-binding protein 1) , which is also involved in translation, using the yeast two-hybrid system. They confirmed this with in vitro assays and in mammalian cells. They believe this interaction between the two proteins may be physiologically relevant because in in vitro assays with a mutated form of BRCA1 the interaction was not observed. In addition RNA interference experiments to reduce the expression of BRCA1 resulted in a decrease in cellular translation. And - overexpression of BRCA1 increased translation activity.

Other studies have indicated that there may be a connection between translation and cancer. Specifically some translation initiation factors such as eIF4E have been linked to malignancy. The specific role of BRCA1 in translation and in tumor suppression is not yet clear, but this study suggests an additional mechanism that might be involved.

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