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Medicine

Taking apart a cancer protein

Nature volume 426, pages 512–513 (2003)Cite this article

Generation of a particular 'fusion' protein is characteristic of one type of leukaemia. But is it in fact the cleavage of this protein into smaller parts that is important? Provocative new findings suggest that it is.

Cancers develop when genetic mistakes accumulate, causing cells to proliferate unchecked and to show a reluctance to die when required. In many human leukaemias, one of the initial genetic errors is a chromosomal translocation: one part of a chromosome fuses with another, creating a composite gene with unusual properties. A well-known example of this occurs in acute promyelocytic leukaemia (APL), a cancer in which promyelocytes — a type of bone-marrow cell that produces certain white blood cells — accumulate in the bone marrow and blood. In most patients with APL, the cancerous cells harbour a chromosome translocation that fuses the promyelocytic leukaemia (PML) gene to the gene for retinoic acid receptor-α (RARα), giving rise to two fusion proteins: PML–RARα and RARα–PML1. It had been thought that full-length PML–RARα is required for this cancer to develop. Writing in Cell, however, Lane and Ley2 challenge this concept. They find that this fusion protein is cleaved at several positions by neutrophil elastase — and that eliminating this enzyme in mice offers some protection from APL.

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Figure 1: Hypothetical role of the PML–RARα fusion protein in acute promyelocytic leukaemia (APL).

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Authors and Affiliations

  1. Departments of Medicine and of Pathology, Molecular Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Pier Paolo Scaglioni & Pier Paolo Pandolfi

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  1. Pier Paolo Scaglioni
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  2. Pier Paolo Pandolfi
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Correspondence to Pier Paolo Pandolfi.

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Paolo Scaglioni, P., Paolo Pandolfi, P. Taking apart a cancer protein. Nature 426, 512–513 (2003). https://doi.org/10.1038/426512a

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