Some cells divide often (think skin cells), while some, such as most brain cells, almost never do. So it stands to reason that cell division must be precisely regulated – an error at any of several transitions along the way can result in developmental problems or out-of-control cell proliferation, the hallmark of cancer. To assure that the cell cycle – the cell’s process of duplicating its DNA and dividing into two identical ‘daughter’ cells – goes smoothly, a large network of proteins tells other proteins what to do and when to do it. In order to better understand cancerand other diseases, it’s important to map out exactly how the cell cycle works.A new study led by Dr. Ze’ev Ronai, associate director of Sanford-Burnham’s National Cancer Institute-designated Cancer Center, and postdoctoral researcher Dr. Gustavo Gutierrez reveals a new player in cell cycle control. This study, which appeared online in Nature Cell Biology on June 27, showed that JNK, a protein already well known for other reasons, also regulates the cell cycle.

“This was totally unexpected of JNK,” Dr. Gutierrez explained. “We already knew that JNK helps cells respond to stress, such as damage caused by ultraviolet radiation. We thought we already knew how the major components of the cell cycle were regulated. This study really changes the thinking by connecting the two.”

On the molecular level, JNK influences cellular functions by tagging other proteins with a phosphate chemical group (a process known as phosphorylation), a common mechanism cells use to turn enzymes on and off. Phosphorylation is so important, in fact, that when JNK goes awry, a number of different disorders can result, such as cancer, diabetes, or neurodegenerative diseases.

The part JNK plays in controlling the cell cycle is completely new. In this study, JNK activity was found to regulate the function of one of the major drivers of the cell cycle, a protein complex known as the APC/C. According to this and related research recently published by Dr. Gutierrez and Dr. Ronai in the Journal of Biological Chemistry, JNK acts like an assembly line inspector; its presence and activity ensures that the cell cycle moves along smoothly. Any problems push JNK to halt the process at certain ‘checkpoints’. If all systems look good, the cell cycle progresses. If not, minor damage is fixed or, if beyond repair, the whole process is scrapped.

“Certain situations where JNK is hyperactive, as seen in some human tumors, might also influence the cell cycle and promote genomic instability,” said Dr. Ronai. “Our laboratory is now assessing this possibility using a mouse model that was engineered based on these new discoveries.”

“I think these findings will open a whole new chapter in both cell cycle research and the understanding of the JNK pathway,” Dr. Gutierrez concluded.