title: Integrin signaling via FAK-Src controls cytokinetic abscission by decelerating PLK1 degradation and subsequent recruitment of CEP55 at the midbody.
abstract: Adhesion to extracellular matrix is required for cell cycle progression through the G1 phase and for the completion of cytokinesis in normal adherent cells. Cancer cells acquire the ability to proliferate anchorage-independently, a characteristic feature of malignantly transformed cells. However, the molecular mechanisms underlying this escape of the normal control mechanisms remain unclear. The current study aimed to identify adhesion-induced reactions regulating the cytokinesis of non-transformed human fibroblasts.The adhesion-dependent control of cytokinesis was found to occur at a late stage close to the abscission, during which the endosomal sorting complex required for transport (ESCRT) severs the thin intercellular bridge connecting two nascent daughter cells. CEP55, a key protein involved in the abscission process, was localized at the midbody in both adherent and non-adherent fibroblasts, but it was unable to efficiently recruit ALIX, TSG101, and consequently the ESCRT-III subunit CHMP4B was missing in the non-adherent cells. PLK1, a kinase that prevents premature recruitment of CEP55 to the midbody, disappeared from this site more rapidly in the non-adherent cells. A FAK-Src signaling pathway downstream of integrin-mediated cell adhesion was found to decelerate both PLK1 degradation and CEP55 accumulation at the midbody. These data identify the regulation of PLK1 and CEP55 as steps where integrins exert control over the cytokinetic abscission.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Siamak A
authors.initials: SA
authors.lastname: Kamranvar
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Deepesh Kumar
authors.initials: DK
authors.lastname: Gupta
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Immunology, Genetics and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Johansson
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D048749:Cytokinesis; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*; D000097869:Polo-Like Kinase 1; D000099177:Tsg101 Protein
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016023:Integrins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D019061:src-Family Kinases; D000097869:Polo-Like Kinase 1; D000099177:Tsg101 Protein; C505378:Cep55 protein, human; C117020:PDCD6IP protein, human
keywords: CEP55; FAK; PLK1; cytokinesis; integrin