Up-Regulation of Cdc37 Contributes to Schwann Cell Proliferation and Migration After Sciatic Nerve Crush

Abstract

Cell division cycle protein 37 (Cdc37), a molecular chaperone takes part in a series of cellular processes including cell signal transduction, cell cycle progression, cell proliferation, cell motility, oncogenesis and malignant progression. It can not only recruit immature protein kinases to HSP90 but also work alone. Cdc37 was reported to be associated with neurogenesis, neurite outgrowth, axon guidance and myelination. However, the roles of Cdc37 on Schwann cells (SC) after peripheral nerve injury (PNI) remain unknown. In this study, we found that the expression of Cdc37 increased and reached the peak at 1 week after sciatic nerve crush (SNC), which was consistent with that of proliferation cell nuclear antigen. Immunofluorescence verified that Cdc37 co-localized with SC in vivo and in vitro. Intriguingly, Cdc37 protein level was potentiated in the model of TNF-α-induced SC proliferation. Moreover, we found that Cdc37 silencing impaired proliferation of SC in vitro. Moreover, Cdc37 suppression attenuated kinase signaling pathways of Raf-ERK and PI3K/AKT which are crucial cell signaling for SC proliferation. Finally, we found that Cdc37 silencing inhibited SC migration in vitro. In conclusion, we demonstrated that the way Cdc37 contributed to SC proliferation is likely via activating kinase signaling pathways of Raf-ERK and PI3K/AKT, and CDC37 was also involved in SC migration after SNC.

Inhibition of Cdc37 Ameliorates Arthritis in Collagen-Induced Arthritis Rats by Inhibiting Synoviocyte Proliferation and Migration Through the ERK Pathway

“…In addition, Cdc37 could mediate cell growth and migration during Drosophila wound healing(36). Meanwhile, Cdc37 contributed to Schwann cell proliferation and migration after sciatic nerve crush (19). Combining the above results, we can speculate that Cdc37 cannot be neglected for cell cycle regulation, cell proliferation, and migration.…”

“…However, while Cdc37 is involved in a variety of diseases, the biological function of Cdc37 in RA is uncertain. Based on our group's previous investigations on the Cdc37 biological function of Schwann cell proliferation and migration in sciatic nerve crush (19). Therefore, we hypothesized that Cdc37 may also be involved in RA development and progression.…”

Hsp90 Activity Is Necessary for the Maturation of Rabies Virus Polymerase

“…Xu et al reported an unusually high expression of Hsp90 and it Cdc37 in N2a cells infected with the RABV HEP-Flury strain [16]. The e sion of these proteins was observed in proliferating cells, in cancers, or d generation [19][20][21][22]. However, despite the universal dependence of virus Figure 6.…”

“…in N2a cells infected with the RABV HEP-Flury strain [16]. The elevated expression of these proteins was observed in proliferating cells, in cancers, or during tissue regeneration [19][20][21][22].…”

Therapeutic Potential of the Hsp90/Cdc37 Interaction in Neurodegenerative Diseases

“…Kinase interaction with Hsp90 generally promotes kinase stabilization and activity (Luo et al, 2017; Bachman et al, 2018). The Hsp90 co-chaperone, Cdc37, is a ubiquitous protein that is required for efficient Hsp90-mediated maturation of kinases, such as CDK5, extracellular regulated kinase (ERK), and protein kinase B (Akt), by aiding their partnership with Hsp90 (Dey et al, 1996; Stepanova et al, 1996; Jinwal et al, 2011; Smith et al, 2015; Keramisanou et al, 2016; Wang et al, 2016; Verba and Agard, 2017; Liu et al, 2018). Strong Hsp90-Cdc37 binders have been characterized to be less thermodynamically stable on their own, whereas clients that are more stable have reduced dependence on Hsp90/Cdc37 for maturation (Taipale et al, 2012; Verba and Agard, 2017).…”