title: CDK1-mediated phosphorylation of Abi1 attenuates Bcr-Abl-induced F-actin assembly and tyrosine phosphorylation of WAVE complex during mitosis.
abstract: Coordinated actin remodeling is crucial for cell entry into mitosis. The WAVE regulatory complex is a key regulator of actin assembly, yet how the WAVE signaling is regulated to coordinate actin assembly with mitotic entry is not clear. Here, we have uncovered a novel mechanism that regulates the WAVE complex at the onset of mitosis. We found that the Bcr-Abl-stimulated F-actin assembly is abrogated during mitosis. This mitotic inhibition of F-actin assembly is accompanied by an attenuation of Bcr-Abl-induced tyrosine phosphorylation of the WAVE complex. We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis. The Abi1 phosphorylated on serine 216 displayed greatly reduced tyrosine phosphorylation in the hematopoietic cells transformed by Bcr-Abl. Moreover, a phosphomimetic mutation of serine 216 to aspartic acid in Abi1 was sufficient to attenuate Bcr-Abl-induced tyrosine phosphorylation of the WAVE complex and F-actin assembly. Ectopic expression of Abi1 with serine 216 mutations interfered with cell cycle progression. Together, these data show that CDK1-mediated phosphorylation of serine 216 in Abi1 serves as a regulatory mechanism that may contribute to coordinated actin cytoskeleton remodeling during mitosis.
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106; State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China.
authors: Chunmei
authors: C
authors: Zhuang
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106.
authors: Hongxing
authors: H
authors: Tang
authors: Department of Surgery, Texas Tech University Health Sciences Center, Amarillo, Texas 79106.
authors: Sharmila
authors: S
authors: Dissanaike
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106; Department of Stem Cell Transplant Program, Texas Tech University Health Sciences Center, Amarillo, Texas 79106.
authors: Everardo
authors: E
authors: Cobos
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106.
authors: Yunxia
authors: Y
authors: Tao
authors: Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas 79106; Department of Stem Cell Transplant Program, Texas Tech University Health Sciences Center, Amarillo, Texas 79106. Electronic address: zonghan.dai@ttuhsc.edu.
authors: Zonghan
authors: Z
authors: Dai
mesh_terms: D000199:Actins / Q000737:chemistry*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D016203:CDC2 Protein Kinase / Q000737:chemistry* / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008938:Mitosis; D010766:Phosphorylation; D014443:Tyrosine / Q000737:chemistry*
chemical_list: C513733:ABI1 protein, human; C513734:Abi1 protein, mouse; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D014443:Tyrosine; D016044:Fusion Proteins, bcr-abl; D016203:CDC2 Protein Kinase