title: 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.
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan; Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, 464-8651, Japan.
authors: Hiroyuki
authors: H
authors: Makihara
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan.
authors: Hironori
authors: H
authors: Inaba
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors: Atsushi
authors: A
authors: Enomoto
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan.
authors: Hiroki
authors: H
authors: Tanaka
authors: Division of Molecular and Cell Biology, Shigei Medical Research Institute, Okayama, 701-0202, Japan.
authors: Yasuko
authors: Y
authors: Tomono
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors: Kaori
authors: K
authors: Ushida
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, 464-8651, Japan.
authors: Mitsuo
authors: M
authors: Goto
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, 464-8651, Japan.
authors: Kenichi
authors: K
authors: Kurita
authors: Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
authors: Yoshihiro
authors: Y
authors: Nishida
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan; Department of Physiology, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan.
authors: Kousuke
authors: K
authors: Kasahara
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan; Department of Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. Electronic address: hgoto@aichi-cc.jp.
authors: Hidemasa
authors: H
authors: Goto
authors: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan; Department of Physiology, Mie University School of Medicine, Tsu, Mie, 514-8507, Japan. Electronic address: minagaki@doc.medic.mie-u.ac.jp.
authors: Masaki
authors: M
authors: Inagaki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D003893:Desmin / Q000378:metabolism*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology
chemical_list: D003893:Desmin; D050505:Mutant Proteins; D010768:Phosphoserine; D016203:CDC2 Protein Kinase
keywords: Cdk1; Desmin; Intermediate filament; Mitosis; Phosphorylation