LA JOLLA, Calif., July 14, 2010 - Put simply, a tumor is the result of out-of-control cell growth. To assure that the cell cycle - the cell's process of duplicating itself to make more cells - goes smoothly, a large network of proteins tells other proteins what to do and when to do it. When any of these layers of protein regulation fail, cell growth can get out of hand. A new study led by Ze'ev Ronai, Ph.D., associate director of Sanford-Burnham's National Cancer Institute-designated Cancer Center, reveals a new player in cell cycle control. These findings, which appeared online in Nature Cell Biology on June 27, showed that JNK, a protein already well known for other duties, also regulates the cell cycle.
"This was totally unexpected of JNK," explained Gustavo Gutierrez, Ph.D., postdoctoral researcher in Dr. Ronai's laboratory and first author of the study. "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 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."
This study was supported by grants from the National Cancer Institute, part of the National Institutes of Health (NIH), and the Sass Foundation. For more information about Sanford-Burnham research, visit http://beaker.sanfordburnham.org.
Original paper: Gutierrez GJ, Tsuji T, Chen M, Jiang W, Ronai ZA. Interplay between Cdh1 and JNK activity during the cell cycle. Nature Cell Biology. 2010 Jul;12(7):686-95.
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 - 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.
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