LAUSR

We and other research teams have been conducting studies on BAG3 protein for several years. BAG3 was first described as a co‐chaperone of HSP70 in 1999 (by Takayama et al. DOI: 10.1074/jbc.274.2.781) and its interactions were soon associated with crucial mechanisms that sustain cell survival in cancer cells. Thereafter, the field of BAG3 protein, due to growing evidence of its stress‐inducible and multifunctional nature, became very attractive and many other groups started to investigate BAG3‐regulated mechanisms in human cells. It was our honor to help collect and prepare excellent reviews and articles appearing in this special issue on “The co‐chaperone BAG3: orchestrator of the cellular task force in response to stress,” which reflects the growing interest in BAG3 studies from various points of view. Indeed, this fascinating protein was described also as a potential biomarker and a therapeutic target in cardiovascular and oncological diseases. And, we are sure that much is still to come. Members of the BAG family of proteins are central elements in cellular protein homeostasis and BAG3, in particular, is a pivotal player in degenerative processes, where protein quality control processes including autophagy, drive cell adaptation to environmental changes. A first original contribution by Baeken and Behl (10.1002/jcb.29925) gave us a novel point of view on BAG3 activities, looking for its connections with other BAG family proteins throughout evolution. An original article in the cancer field came by Linder et al. (10.1002/jcb.30073), which described BAG3 in glioblastoma multiforme and triple‐negative breast cancer as a negative regulator of ciliogenesis, a process that, when slowed down, favors cancer cell migration. One other contribution came by De Marco et al. (10.1002/jcb.30171), which disclosed that tumor cell‐secreted BAG3 directly promotes fibroblasts’ activation and described a correlation between BAG3 levels and survival in fibrotic cancer patients. The same topic was complemented by the Difrusine et al. (10.1002/jcb.30172) article, in which key cytokines involved in pancreatic cancer cells migration were shown to be induced and released by BAG3‐activated fibroblasts. In cancer diseases, HSP70/BAG3 interaction was proposed as a therapeutic target. Martin et al. (10.1002/jcb.30140) documented that the use of JG98, a small molecule able to disrupt the complex, has detrimental effects on cardiomyocytes, by increasing apoptosis and reducing autophagic flux. Of note, this contribution pointed out the importance of narrowing BAG3 targeting to specific functions in human diseases. BAG3 was also described in the past as a host cell factor able to modulate viral infections; here, a novel insight in the field came by Basu et al. (10.1002/jcb.29953). This paper described, by an in silico analysis, possible interactions between BAG3 and several pathogen proteins, thus opening perspectives in studies aimed to characterize the role of BAG3 in bacterial propagation in humans. Brilliant reviews also gave the finishing touch to our Special Issue. Sherman and Gabai (10.1002/jcb.30111) and Heng (10.1002/jcb.29952) nicely reviewed BAG3‐ regulated cellular mechanisms in health and disease, while Marzullo et al. (10.1002/jcb.30123) proposed the protein intrinsic disorder model as a way to explain BAG3 promiscuity and multifunctionality. Finally, Maffioli et al. (10.1002/jcb.30192) contributed with a state of the art and perspectives on the possible use of BAG3 protein as a biomarker in cardiovascular diseases, and Roperto (10.1002/jcb.30193) resumed BAG3 studies conducted in papilloma virus‐induced urinary bladder carcinoma in cattle.