Ankyrin Repeat-Rich Membrane Spanning (ARMS)/Kidins220 Scaffold Protein Regulates Neuroblastoma Cell Proliferation through p21

• Published in: Molecules and cells Vol. 37; no. 12; pp. 881 - 887
• Main Authors: Jung, Heekyung, Shin, Joo-Hyun, Park, Young-Seok, Chang, Mi-Sook
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.12.2014; 한국분자세포생물학회
• Subjects: Animals; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Neuroblastoma - metabolism; Neuroblastoma - pathology; Phosphorylation; Signal Transduction; 생물학; scaffold protein; cyclin; neurotrophin; proliferation; cell cycle
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2014.0182

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.