title: Ankyrin repeat-rich membrane spanning (ARMS)/Kidins220 scaffold protein regulates neuroblastoma cell proliferation through p21.
abstract: Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the G1 phase. The ankyrin repeat-rich membrane spanning (ARMS) scaffold protein, also known as kinase D-interacting substrate of 220 kDa (Kidins 220), has been previously identified as a prominent downstream target of neurotrophin and ephrin receptors. Many studies have reported that ARMS/Kidins220 acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems. However, the role of ARMS/Kidins220 in cell proliferation and cell-cycle progression has never been investigated. Here we report that knockdown of ARMS/Kidins220 inhibits mouse neuroblastoma cell proliferation by inducing slowdown of cell cycle in the G1 phase. This effect is mediated by the upregulation of a CDK inhibitor p21, which causes the decrease in cyclin D1 and CDK4 protein levels and subsequent reduction of pRb hyperphosphorylation. Our results suggest a new role of ARMS/Kidins220 as a signaling platform to regulate tumor cell proliferation in response to the extracellular stimuli.
authors.affiliation: Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
authors.forename: Heekyung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Oral Anatomy, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: C530105:Ccnd1 protein, mouse; C544017:Kidins220 protein, mouse; D008565:Membrane Proteins; D019938:Cyclin D1; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4
keywords: cell cycle; cyclin; neurotrophin; proliferation; scaffold protein