ENTRY OF PROTEIN TOXINS INTO THE CYTOSOL

OLSNES, S.(1)

(1)Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway

Protein toxins like bacterial diphtheria toxin, cholera toxin, anthrax toxin, Shiga toxin and the plant toxin ricin exert their action in the cytosol by enzymatically modifying vital  proteins. The toxin start their route into the cells by binding to cell surface receptors followed by endocytosis of the toxin-receptor complex. Diphtheria toxin and anthrax toxin are equipped with their own translocation devices facilitating transport of the enzymatically active toxin subunit to the cytosol. Cholera toxin, Shiga toxin and ricin lack translocation devices and are dependent on cellular functions for their translocation. They are transported retrograde through the Golgi apparatus to the endoplasmic reticulum where they are translocated to the cytosol by the misfolded protein degradation pathway. Once in the cytosol, the enzymatically active toxin subunit is able to avoid degradation by the proteasomes. An overview over the field will be given together wit a critical assessment of the evidence. Finally experiments will be described that indicate that also certain growth factors enter the cytosol in related ways.

CORRESPONDENCE TO:

OLSNES, S., Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway, Email: sjur.olsnes@labmed.uio.no