Discovery that specific protein modification important in cancer development

Visualising DNA (blue) and HSP70 (green) during cell division shows that methylated HSP70 associates with DNA (top row), but unmethylated HSP70 is distributed throughout the rest of the cell (bottom row). Credit:

All proteins are made from chains of amino acids and their functions can be modified by adding small molecules to specific amino acids. One such modification is the addition of a methyl group, which is made of one carbon and three hydrogen atoms, that is attached to the amino acids lysine or arginine. This methylation occurs in many proteins, but its function is unclear.

Heat-shock protein 70 () is one protein that is methylated on a specific lysine amino acid. HSP70 is found in all animals and plays a role in many biochemical processes within cells. Other HSP70 modifications have been directly linked to diseases such as cancer and Parkinson's disease. Now, an international team, including researchers at the RIKEN Advanced Science Institute, Japan, has demonstrated that lysine methylation has similar implications.

Staining HSP70 with fluorescent markers showed that the methylated protein was concentrated in the chromosomes, while the unmethylated protein was spread throughout the cell, outside of the chromosomes. By capturing the methylated protein from cells and identifying the proteins that came with it, the team found an important interaction with an enzyme called Aurora kinase B (AURKB).

"AURKB is an important protein that promotes cell cycle progression and can encourage cancer ," explains co-author Minoru Yoshida. "Indeed, its expression is often deregulated in cancer and its inhibitors have been developed for ."

AURKB activity was enhanced by its interaction with HSP70, and introducing mutant HSP70 into showed that this interaction altered cell growth: HSP70 methylation accelerated cell growth and division. Having found that levels of methylated HSP70 are higher than normal in cultured and tissue from human cancer patients, the team concluded that the modification of the protein is important in the development of cancer.

Despite these findings, Yoshida says there is still much to understand about HSP70 methylation: "It is necessary to do more detailed analyses of why HSP70 is highly methylated in , how it is specifically localized in the nucleus, and how it activates AURKB," he says. But he also thinks that this work provides a new tool in the battle against the disease. "We expect that methylated HSP70 will be a remarkable new cancer diagnosis marker," he says. "As for therapy, not only AURKB inhibitors but also HSP70 methylation inhibitors or a combination of both will be new chemotherapeutic strategies in future."

More information: Cho, H-S., et al. Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B. Nature Communications 3, 1072 (2012).… c_id=NCOMMS-20120918

Related Stories

Researchers give mutants another chance

date Feb 11, 2009

Researchers at Fox Chase Cancer Center have demonstrated that it might be possible to treat genetic diseases, including some forms of cancer, by "rescuing" the misshapen, useless proteins produced by some mutant genes.

Recommended for you

Spicy treatment the answer to aggressive cancer?

date 11 hours ago

It has been treasured by food lovers for thousands of years for its rich golden colour, peppery flavour and mustardy aroma…and now turmeric may also have a role in fighting cancer.

Cancer survivors who smoke perceive less risk from tobacco

date Jul 02, 2015

Cancer survivors who smoke report fewer negative opinions about smoking, have more barriers to quitting, and are around other smokers more often than survivors who had quit before or after their diagnosis, according to a ...

Melanoma mutation rewires cell metabolism

date Jul 02, 2015

A mutation found in most melanomas rewires cancer cells' metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.