RRC ID 52281
Author Takahashi Y, Tanikawa C, Miyamoto T, Hirata M, Wang G, Ueda K, Komatsu T, Matsuda K.
Title Regulation of tubular recycling endosome biogenesis by the p53-MICALL1 pathway.
Journal Int J Oncol
Abstract p53, one of the most frequently mutated genes in colon cancer, suppresses cancer development through transactivation of its targets. Herein, we conducted a comprehensive analysis of the p53 downstream pathway in colorectal cancer by using multi-omics analysis. Mass spectrometric analysis of HCT116 p53+/+ and HCT116 p53-/- cells treated with adriamycin identified 124 proteins increased by DNA damage in a p53-dependent manner. Further screening using a cDNA microarray and the TCGA database revealed MICALL1 as a novel p53 target, and we identified functional p53 binding motifs located approximately 3000 base pairs upstream of the MICALL1 gene. MICALL1 expression was significantly decreased in colorectal cancer tissues with p53 mutation compared with those without p53 mutation. In response to DNA damage, MICALL1 co-localized with RAB8A and CD2AP at tubular recycling endosomes, whereas these proteins hardly localized at tubular recycling endosomes when p53 or MICALL1 expression was inhibited by siRNA. Our findings show that p53 regulates tubular recycling endosome biogenesis via transcriptional regulation of MICALL1, whose expression is frequently suppressed in colorectal cancer tissues.
Volume 51(2)
Pages 724-736
Published 2017-8-1
DOI 10.3892/ijo.2017.4060
PMID 28714518
MeSH Adaptor Proteins, Signal Transducing / chemistry Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Binding Sites Cell Line, Tumor Colorectal Neoplasms / genetics Colorectal Neoplasms / metabolism* Cytoskeletal Proteins / chemistry Cytoskeletal Proteins / genetics* Cytoskeletal Proteins / metabolism Doxorubicin / pharmacology* Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic / drug effects HCT116 Cells Humans LIM Domain Proteins / chemistry LIM Domain Proteins / genetics* LIM Domain Proteins / metabolism Mass Spectrometry Mutation Oligonucleotide Array Sequence Analysis / methods Proteomics / methods Signal Transduction / drug effects Tumor Suppressor Protein p53 / genetics* rab GTP-Binding Proteins / metabolism
IF 3.899
Times Cited 4
Human and Animal Cells 293T(RCB2202)