Humanizing Protein Splicing
Human immunity uses a posttranslational modification previously shown in
plants and yeast
By Sam Jaffe

James Yang, a surgeon working at the National Cancer Institute in Bethesda,
Md., looked despondently at a patient's chest CT scan in 1998. Most of
Yang's patients have late stage metastasized renal cancer; few of them
survive. By the looks of the scan, this patient was in trouble. Metastasized
tumors bloomed throughout his chest.

One spot on the scan caught Yang's eye, though. While most of the lung
tumors were growing, one had shrunk noticeably since the last scan. Yang
circled the regressing tumor with his grease pen, making a mental note to
ask the thoracic surgeon to save a tissue sample from that odd tumor. The
surgery was successful and the patient lived a few more years before finally
succumbing to his disease. But the CD8+ cytotoxic T cells taken from that
one tumor would go on to serve as the basis for a discovery with
implications for immunology and possibly all of molecular biology.

Yang and his research fellow Ken-Ichi Hanada identified a cellular process
in that tissue sample that had never before been seen in vertebrates, no
less in humans.1 Protein splicing was occurring in the cells of that
regressing tumor. In an immunological trick, some cellular mechanism removed
multiple amino acids from a protein and re-ligated the open carboxyl and
amino termini to produce an antigen for presentation. Though such protein
editing events have been noted in bacteria, archaea, yeast, and plants, this
is the first evidence of protein splicing in vertebrates

Read the rest at The Scientist.com
http://www.the-scientist.com/yr2004/jun/research2_040607.html

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