Major Proteins Tied to Cancer and Aging

This discovery focuses on the makeup and assembly of major chromosomal protein complexes involved in turning off reproduction of aging cells.

Aging cells, also known as senescent cells, are no longer capable of dividing but stay metabolically active. "Accumulation of senescent cells over time appears to contribute to changes in tissue form and function commonly associated with aging, like the skin changes that occur between childhood and old age,” stated Peter D. Adams, Ph.D., from Fox Chase Cancer Center, in Philadelphia, PA, USA (www.fccc.edu)

Most normal human cells undergo a finite number of cell divisions but are gradually arrested, either through senescence or final differentiation. Differentiation is a process in which a proliferating cell stops growing and develops into a cell with a particular function, such as a neuron or a liver cell. Senescence is a permanent stage in a cell's life cycle and may underlie the human aging process and have an effect on diseases of aging, such as adult cancers.

"Most importantly, the failure of cells to stop growing through differentiation or senescence can lead to the uncontrolled growth of cancer,” Dr. Adams said. Both differentiation or senescence involve reorganization of chromatin structure--the complex of RNA, DNA, and proteins, called histones, in the cell nucleus.

Earlier studies have demonstrated that as cells reach senescence, an alteration in chromatic structure called senescence-associated heterochromatin foci (SAHF) silences the genes that trigger the cells' growth. This discovery reveals the process of SAHF formation. SAHF are domains of tightly packed chromatin that repress activity of the genes that normally trigger cell proliferation. The Fox researchers have identified at least three proteins in the cell that contribute to the formation of SAHF. These proteins are called ASF1a, HIRA, and promyelocytic leukemia (PML). Scientists have known for a while that PML suppresses the formation of this type of leukemia, but do not know why.

This research suggests the possibility that PML arises because the PML protein is not able to do its job in forming SAHF. If this is true, this study might help in the design of therapeutic drugs to treat cancer patients and even lessen some aspects of aging. Additional study in this field will define the molecular details by which HIRA, PML, and ASF1 and formation of SAHF may also be a factor in other human cancers.




Related Links:
Fox Chase Cancer Center