When Tumor Suppression Fails

Science Daily features an article titled Gene Helps Protect Tumor Suppressor In Breast Cancer. Quoting from the first paragraph:

Scientists at The University of Texas M. D. Anderson Cancer Center have discovered a gene that protects PTEN, a major tumor-suppressor that is reduced but rarely mutated in about half of all breast cancers.

Research indicates that cancers can result from genetic malfunctions involving multiple genes and their end products. But it may have nothing to do with a mutation affecting the function of a particular gene known to be essential in inhibiting tumors. The mutation may occur in a regulatory gene which impacts the expression of the essential gene.

The linked article identifies PTEN as a tumor-suppresor and a gene dubbed Rak as a regulator of PTEN. Degradation of proteins is a normal cellular function. Protein levels should be optimized to match function requirements. If too many proteins are degraded then not enough may be available to perform vital cellular functions. The destruction of PTEN proceeds when PTEN binds with the enzyme NEDD4-1 which leads to an attachment by a protein known as ubiquitin. When this occurs destruction of PTEN is brought about by a complex of proteins called the ubiquitin proteasome complex.

So what does Rak do? It can prevent PTEN degradation by attaching a phosphate group to PTEN. This in turn prevents NEDD4-1 from binding to PTEN. With so many proteins involved in a regulatory process one can see how the malfunction of just one of them can have severe adverse health effects.

A researcher also noted that Rak has a role in preventing DNA damage. It appears to be a multi-purpose gene with genomic integrity as one of its roles.