Recent work from Pandithage et al. reveals a new pathway for controlling cell movement that involves a cancer enabler and a member of a protein family best known for boosting longevity.
The researchers chanced on the discovery while investigating the oncogene Myc, which is overactive in many tumors. Myc activates cyclin E and cyclin-dependent kinase (CDK)—a protein power couple that pushes cells through the cell cycle. The team wanted to determine what lies downstream of this pair.
One of the pair's targets, they found, is SIRT2, a member of the sirtuin protein family. Sirtuins take part in everything from insulin secretion to transcription and can extend life span in organisms such as nematodes and yeast. The cyclin E/CDK pair and other cyclin/CDK combinations phosphorylate SIRT2 to shut it down, the team found.
SIRT2 cleaves acetyl groups off histones and α-tubulin. As a result of its tubulin effects, SIRT2 destabilizes microtubules. The group found that by preventing microtubule extension, SIRT2 stopped tumor cells from getting a good grip on the substrate—a necessity for crawling. Thus by indirectly shutting off SIRT2, Myc might prompt the migration of cancer cells.
SIRT2 also blocked the protrusion of neurites from brain neurons. The work indicates that this enzyme helps maintain the status quo in cells by regulating microtubule stability. Recent studies implicate SIRT2 in neurodegeneration, which suggests that this pathway could also be involved in illnesses such as Parkinson's disease.