“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.