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Maintenance of cellular health requires the proper regulation of E3 ubiquitin ligases. The E3 ligase CHIP is canonically regulated by its interactions with the molecular chaperones Hsp70 and Hsp90, which focus CHIP's ubiquitination activity on misfolded proteins. Here, we report a chaperone-independent interaction of CHIP with the membrane-anchored protein CHIC2, which strongly attenuates CHIP's ligase activity. We show that CHIC2 outcompetes abundant, cytosolic chaperones through its exquisite CHIP selectivity, rather than through enhanced affinity. In proteomic experiments, we find that CHIC2 knockout phenocopies CHIP knockout in certain cell types, implying that chaperone-independent interactions can sometimes predominate CHIP's functions. Furthermore, loss of the CHIP-CHIC2 interaction induces neurodegeneration and shortens lifespan in C. elegans, demonstrating that formation of this chaperone-independent complex is important in animals. We propose that CHIC2 attenuates CHIP activity at the membrane, offering a novel mechanism by which this ubiquitin ligase can be regulated.

I am very aware that there are some whose presence at this conference makes my paper a 'sermon' to the converted. For this I apologise. (I have, in fact, been warned by an already long-time practitioner of Africanisation, that, by presenting this paper, I will be re-inventing the wheel-my experience at 'English' conferences, however, tells me otherwisel) I do, however, feel that the time has come for open discussion on the necessary transformation of English Studies in the 'new' South Africa. There will have to be a transformation of English Studies, if it is not to become at best a useless quaint colonial relic, or at worst an instrument of disempowerment. Not only does the myth of a 'standard' language need to be demythologised, but so too the myths of a 'standard' critical practice, and a 'standard' point of view-in fact the whole myth surrounding the term 'standard'. All 'standards' are in fact rooted in the validation of our ideology-Western civilization. Whether we acknowledge it or not, we are in fact privileging and entrenching-and enforcingl-our particular historical, cultural and socio-political system at the expense of other systems. As second language students are likely to be the new student population of English departments in the very near future, it is perhaps opportune to comment on some of the still 'negative' attitudes prevailing towards them in some quarters and to report briefly on the creativity in course design and on the changing attitudes to English 'competency' of which I have become aware. Unfortunately, most innovators are working in isolation, not only from other English departments, but even within their own departments. It liould be to everyone's advantage, and more cost and time effective http://spilplus.journals.ac.za/

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