Desmin phosphorylation by Cdk1 is required for efficient separation of desmin intermediate filaments in mitosis and detected in murine embryonic/newborn muscle and human rhabdomyosarcoma tissues

Abstract

Desmin is a type III intermediate filament (IF) component protein expressed specifically in muscular cells. Desmin is phosphorylated by Aurora-B and Rho-kinase specifically at the cleavage furrow from anaphase to telophase. The disturbance of this phosphorylation results in the formation of unusual long bridge-like IF structures (IF-bridge) between two post-mitotic (daughter) cells. Here, we report that desmin also serves as an excellent substrate for the other type of mitotic kinase, Cdk1. Desmin phosphorylation by Cdk1 loses its ability to form IFs in vitro. We have identified Ser6, Ser27, and Ser31 on murine desmin as phosphorylation sites for Cdk1. Using a site- and phosphorylation-state-specific antibody for Ser31 on desmin, we have demonstrated that Cdk1 phosphorylates desmin in entire cytoplasm from prometaphase to metaphase. Desmin mutations at Cdk1 sites exhibit IF-bridge phenotype, the frequency of which is significantly increased by the addition of Aurora-B and Rho-kinase site mutations to Cdk1 site mutations. In addition, Cdk1-induced desmin phosphorylation is detected in mitotic muscular cells of murine embryonic/newborn muscles and human rhabdomyosarcoma specimens. Therefore, Cdk1-induced desmin phosphorylation is required for efficient separation of desmin-IFs and generally detected in muscular mitotic cells in vivo.

Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle

“…6b). Cyclin-dependent kinase-1 (Cdk-1) is responsible for this phosphorylation [43]: consistently, it was more active in Drp/MC muscle at P7 (Fig. 6c).…”

Intermediate filaments in cardiomyopathy

“…Most of PTMs cause disassembly of desmin network, with the exception of ubiquitination which leads to its degradation. Among other enzymes (PKA, PKC, PAK, CaMKII) (Winter et al 2014), desmin is phosphorylated by Rho kinase (Inada et al 1998), Aurora-B (Kawajiri et al 2003), and by Cdk1 (Makihara et al 2016), all PTMs required for efficient separation of desmin-IFs in mitosis (Inada et al 1999;Kawajiri et al 2003).…”

Identification and characterization of the CDK1-BMAL1-UHRF1 pathway driving tumor progression

“… 47 , 48 , 49 The kinase activity of CDK1 plays a regulatory role in various types of tumors, including bladder cancer, 50 prostate cancer, 51 gastric cancer, 52 breast cancer, 53 colorectal cancer, 54 and rhabdomyosarcoma. 55 Generally, the kinases catalyze the phosphorylation of substrates. In contrast, our study showed that CDK1 regulated BMAL1 S42 dephosphorylation, leading to tumor progression.…”