Missing link in cell division discovered

26 July 2010

Researchers from The George Washington University Medical Center have identified a protein that plays a crucial role in cell division and is over-expressed in breast cancer.

The discovery promises to revolutionize the understanding of key aspects of cellular lifecycle and offers a new avenue for cancer treatment.

The protein, Arpc 1b, serves as both an activator as well as a substrate for Aurora A, an enzyme that plays a central role in cellular reproduction in normal cells but is overexpressed in several cancers. This represents perhaps the earliest step in mitosis and serves as the missing link regarding the role this protein plays in starting the cell cycle and what keeps the process in balance. The authors discovered that Arpc1b also exists as a standalone protein and believe that it might also play an independent role outside its established contribution to actin machinery.

More than just an observation of how cells divide, this discovery also offers a potential target for pharmaceutical therapy. Both Aurora A and Arpc1b are over-expressed in breast cancers. Pharmaceutical inhibitors targeting Aurora A are currently available and thus, could be combined with other future targeting strategies. The researchers discovered that an over-expression of Arpc1b promotes tumorigenic properties of breast cancer cells. Scientists believe that if they can someday find a means of suppressing the activity of Arpc 1b in cancer cell, the balance could be restored to this dynamic yet tightly regulated biological event.

The discovery, reported in the article "Arpc 1b, a centrosomal protein, is both an activator and substrate of Aurora A," furthers the science world's understanding of what happens during the fundamental process of mitosis, when cells divide. The article was published in the current issue of The Journal of Cell Biology.

"This represents a crucial moment when the division of genetic material is still equally distributed. An even exchange is critical for stable genetic changes," said Rakesh Kumar, Ph.D., chair of the GW Department of Biochemistry and Molecular Biology. In mitosis, cells begin to divide and genetic material coalesces around separate poles to form new cells. If all goes well that material is evenly distributed and two genetically identical "daughter cells" are formed. If something goes awry, however, it can result in the cascading production of aberrant cells with unequal and less ordered DNA and possibly cancer.

"This discovery is the result of persistence and the commitment to scientific breakthrough," said Dr. Kumar. "Asking a question and staying involved until you find the answer to close the loop is critical in scientific discovery." In this case the earliest piece of data used here was obtained in 2001.

To learn more about this research, view The Journal of Cell Biology article: http://jcb.rupress.org/content/early/2010/06/30/jcb.200908050.full