The heat shock protein 40kDa (HSP40/DNAJ) co-chaperones constitute the largest and most diverse sub-group of the heat shock protein (HSP) family. DNAJ are widely accepted as regulators of HSP70 function, but also have roles as co-chaperones for the HSP90 chaperone machine, and a growing number of biological functions that may be independent of either of these chaperones. The DNAJ proteins are differentially expressed in human tissues and demonstrate the capacity to function to both promote and suppress cancer development by acting as chaperones for tumour suppressors or oncoproteins. We review the current literature on the function and expression of DNAJ in cancer, stem cells and cancer stem cells. Combining data from gene expression, proteomics and studies in other systems, we propose that DNAJ will be key regulators of cancer, stem cell and possibly cancer stem cell function. The diversity of DNAJ and their assorted roles in a range of biological functions means that selected DNAJ, provided there is limited redundancy and that a specific link to malignancy can be established, may yet provide an attractive target for specific and selective drug design for the development of anti-cancer treatments.
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