There are processes in the human body that can suppress the growth and proliferation of cancer cells. These mechanisms, including those involving the tumor suppressor protein p53, are widely studied due to their critical role in disease. Through studies of proteins that regulate p53, scientists at St.
Jude Children's Research Hospital have uncoupled a previously unrecognized tumor suppression mechanism. Usually found at low levels in cells, the p14 Alternative Reading Frame protein (p14 ARF ) is expressed at higher levels under oncogenic stress and activates p53. The researchers identified an alternative tumor suppression mechanism for p14 ARF , showing how condensate formation and ribosome production disruption contribute to the process.
The findings were published today in Nature Communications . The researchers demonstrated that increased expression of p14 ARF causes the protein to phase separate with other cellular components. This occurs within the nucleolus, a membraneless compartment in the nucleus of cells responsible for ribosome production.
In the nucleolus, p14 ARF binds to and phase separates with nucleophosmin, an essential protein for ribosome production, creating a gel-like state, leading to decreased nucleophosmin dynamics, stalled ribosome biogenesis and cell toxicity. The process, kickstarted by p14 ARF , thus represents a likely alternative tumor suppressive pathway. p14 ARF gums up the works in the nucleolus "p14 ARF is normally expressed at very low level.