title: Filamin A stimulates cdc25C function and promotes entry into mitosis.
abstract: The activity of the dual specificity phosphatase cdc25C is required for mitotic progression though the mechanisms by which cdc25C is activated prior to mitosis in human cells remain unclear. The data presented herein show that the actin binding protein Filamin A forms a complex with cdc25C in vivo and binds preferentially to the mitotic form of cdc25C. Co-expression of Filamin A with cdc25C results in an increase in PCC induced by cdc25C, while knocking down Filamin A expression reduces the levels of PCC induced by cdc25C overexpression. Further, only a Filamin A fragment that forms a complex with both cdc25C and cyclin B1 and retains the dimerization domain can stimulate the ability of cdc25C to induce PCC. These results suggest that Filamin A provides a platform for the assembly of the cyclin B1-cdk1- cdc25C complex resulting in cdk1 activation and mitotic progression.
authors.affiliation: KS215 Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre Kharghar Node, Navi, Mumbai, India.
authors.forename: Elphine
authors.initials: E
authors.lastname: Telles
authors.forename: Mansa
authors.initials: M
authors.lastname: Gurjar
authors.forename: Ketaki
authors.initials: K
authors.lastname: Ganti
authors.forename: Dipika
authors.initials: D
authors.lastname: Gupta
authors.forename: Sorab N
authors.initials: SN
authors.lastname: Dalal
mesh_terms: D016203:CDC2 Protein Kinase / Q000378:metabolism; D002460:Cell Line; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D019281:Dimerization; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism / Q000502:physiology*
chemical_list: D003285:Contractile Proteins; D056744:Cyclin B1; D064448:Filamins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases