Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome

Adult Cyclin-Dependent Kinase Inhibitor p21 Male Ribosomal Proteins Transcriptional Activation 0301 basic medicine Adolescent Science Kruppel-Like Transcription Factors Apoptosis Article Proto-Oncogene Proteins c-myc 03 medical and health sciences Humans Promoter Regions, Genetic Aged Aged, 80 and over 0303 health sciences Q R Cell Cycle Checkpoints Middle Aged Microarray Analysis Gene Expression Regulation Myelodysplastic Syndromes Medicine Female Signal Transduction
DOI: 10.1038/s41598-017-02403-x Publication Date: 2017-05-18T09:55:26Z
ABSTRACT
Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression associated with abnormal apoptotic resistance in CD34+ cells derived from patients higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced MDS poorly understood. In this study, we showed that reduced expression led to suppressed viability, increased apoptosis G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown control identified an array differentially expressed genes, which, Miz-1, was upregulated transactivation inhibitors p15Ink4b p21Cip1, Miz-1's functional repressor, c-Myc, downregulated. Cells demonstrated consistently c-Myc decreased Miz-1 compared lower-risk patients. conclusion, Miz-1-dependent induction p21Cip1 depressed under conditions elevated expression, leading Because encoded by target gene RPL23/Miz-1/c-Myc regulatory circuit provides feedback loop links efficient c-Myc's function suppress Miz-1-induced Cdk thereby leads
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