Molecular chaperones are essential components of the protein quality control system and maintenance of homeostasis. Heat Shock Protein 70 (HSP70), a highly evolutionarily conserved family of chaperones is a key regulator of protein folding, oligomerisation and prevents the aggregation of misfolded proteins. HSP70 chaperone function depends on the so-called ‘HSP70-cycle', where HSP70 interacts with and is released from substrates via ATP hydrolysis and the assistance of HSP70 co-factors/co-chaperones, which also provide substrate specificity. The identification of regulatory modules for HSP70 allows the elucidation of HSP70 specificity and target selectivity. Here, we discuss how the HSP70 cycle is functionally linked with the cycle of the Ubiquitin-like molecule NEDD8. Using as an example the DNA damage response, we present a model where HSP70 acts as a sensor of the NEDD8 cycle. The NEDD8 cycle acts as a regulatory module of HSP70 activity, where conversion of poly-NEDD8 chains into mono-NEDD8 upon DNA damage activates HSP70, facilitating the formation of the apoptosome and apoptosis execution.
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Cover Image
Cover Image
Depicted as playing cards belonging to the same suit, the paralogous MLL3 and MLL4 lysine methyltransferase (KMT) complexes share a common set of core and auxiliary subunits as well as similar histone methylase functions. On each card, largely divergent processes are described on opposing sides – highlighting the potential capacity of these KMT complexes to participate in both tumor-supportive and tumor-suppressive mechanisms. To understand how MLL3 and MLL4 can regulate such diverse and sometimes contrasting processes, read more in this review article by Wang and colleagues (pp. 1041–1054). Cover artwork created by Marvin Aberin with Biorender.com.
The HSP70 chaperone as sensor of the NEDD8 cycle upon DNA damage
Aymeric P. Bailly, Dimitris P. Xirodimas; The HSP70 chaperone as sensor of the NEDD8 cycle upon DNA damage. Biochem Soc Trans 30 June 2021; 49 (3): 1075–1083. doi: https://doi.org/10.1042/BST20200381
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