Paper in the Journal of Biological Chemistry notes that nuclear import of the p115 CTF is required.
Scientists at Albert Einstein College of Medicine of Yeshiva University say that they have identified a small intracellular protein that helps apoptosis. The culprit is a peptide that is 26 amino acids long and is part of the Golgi apparatus. It exerts its apoptotic action by traveling to the nucleus.
Until about a decade ago, apoptosis was thought to be directed solely by the nucleus and mitochondria of cells. Dennis Shields, Ph.D., a professor in Einstein’s department of developmental and molecular biology for 30 years, who died in December was reportedly the first to show that the Golgi apparatus also plays a role in apoptosis.
A protein called p115 is vital for maintaining the structure of the Golgi. In earlier research, Dr. Shields’ group demonstrated that the Golgi’s p115 protein splits into two pieces early in apoptosis and generates a C-terminal fragment (CTF) of 205 residues, which helps maintain the cell-suicide process.
In the present study, it was shown that early during apoptosis, following the rapid cleavage of p115, endogenous CTF translocated to the cell nucleus and its nuclear import was required to enhance the apoptotic response. Expression of a series of deletion constructs identified a putative alpha-helical region of 26 amino acids, whose expression alone was sufficient to induce apoptosis. Deletion of these 26 residues from the CTF diminished its proapoptotic activity.
These results demonstrate that nuclear import of the p115 CTF is required for it to stimulate the apoptotic response and suggest that its mode of action is confined to the nucleus. The findings are reported in the January 16 issue of the Journal of Biological Chemistry.
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