p97 Is in a complex with cholera toxin and influences the transport of cholera toxin and related toxins to the cytoplasm.

Certain protein toxins, including cholera toxin, ricin, and Pseudomonas aeruginosa exotoxin A, are transported to the lumen of the endoplasmic reticulum where they retro-translocate across the endoplasmic reticulum membrane to enter the cytoplasm. The mechanism of retrotranslocation is poorly understood but may involve the endoplasmic reticulum-associated degradation pathway. The AAA ATPase p97 (also called valosin-containing protein) participates in the retro-translocation of cellular endoplasmic reticulum-associated degradation substrates and is therefore a candidate to participate in the retrotranslocation of protein toxins.

Evidence that the transport of ricin to the cytoplasm is independent of both Rab6A and COPI.

Cholera toxin, Shiga toxin and ricin are examples of protein toxins that require retrograde transport from the Golgi complex into the endoplasmic reticulum (ER) to express their cytotoxic activities and different toxins appear to use different pathways of retrograde transport. Cholera toxin contains the mammalian retrograde targeting signal KDEL and is believed to exploit the coat protein I (COPI) and KDEL receptor-dependent pathway to go from the Golgi complex to the ER. Shiga toxin, however, has no KDEL sequence to specify its inclusion in COPI-coated retrograde vesicles and is believed to use a recently discovered COPI-independent and Rab6A-dependent retrograde pathway to enter the ER.