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ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family. Previously, we have shown that ING5 inhibits invasiveness of lung cancer cells by downregulating EMT-inducing genes. However, the underlying mechanisms remain unclear. The aim of the study was to use integrated approach involving SILAC labeling and mass spectrometry-based quantitative proteomics to quantify dynamic changes of acetylation regulated by ING5 in lung cancer cells. Here, we have found that ING5 has a profound influence on protein lysine acetylation with 163 acetylation peptides on 122 proteins significantly upregulated and 100 acetylation peptides on 72 proteins downregulated by ING5 overexpression. Bioinfomatic analysis revealed that the acetylated proteins upregulated by ING5 located preferentially in nucleus to cytoplasm and were significantly enriched in transcription cofactor activity, chromatin binding and DNA binding functions; while those downregulated by ING5 located preferentially in cytoplasm rather than nucleus and were functionally enriched in metabolism, suggesting diverse functions of ING5 through differentially regulating protein acetylation. Interestingly, we found ING5 overexpression promotes p300 autoacetylation at K1555, K1558 and K1560 within p300 HAT domain, and two novel sites K1647 and K1794, leading to activation of p300 HAT activity, which was confirmed by accelerated acetylation of p300 target proteins, p53 at k382 and histone H3 at K18. A specific p300 HAT inhibitor C646 impaired ING5-increased acetylation of H3K18 and p53K382, and subsequent expression of p21 and Bax. In conclusion, our results reveal the lysine acetylome regulated by ING5 and provide new insights into mechanisms of ING5 in the regulation of gene expression, metabolism and other cellular functions.
Pubmed ID: 29416718 RIS Download
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Service providing functional analysis of proteins by classifying them into families and predicting domains and important sites. They combine protein signatures from a number of member databases into a single searchable resource, capitalizing on their individual strengths to produce a powerful integrated database and diagnostic tool. This integrated database of predictive protein signatures is used for the classification and automatic annotation of proteins and genomes. InterPro classifies sequences at superfamily, family and subfamily levels, predicting the occurrence of functional domains, repeats and important sites. InterPro adds in-depth annotation, including GO terms, to the protein signatures. You can access the data programmatically, via Web Services. The member databases use a number of approaches: # ProDom: provider of sequence-clusters built from UniProtKB using PSI-BLAST. # PROSITE patterns: provider of simple regular expressions. # PROSITE and HAMAP profiles: provide sequence matrices. # PRINTS provider of fingerprints, which are groups of aligned, un-weighted Position Specific Sequence Matrices (PSSMs). # PANTHER, PIRSF, Pfam, SMART, TIGRFAMs, Gene3D and SUPERFAMILY: are providers of hidden Markov models (HMMs). Your contributions are welcome. You are encouraged to use the ''''Add your annotation'''' button on InterPro entry pages to suggest updated or improved annotation for individual InterPro entries.
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View all literature mentionsAn annotation program which aims to provide high-quality Gene Ontology (GO) annotations to proteins in the UniProt Knowledgebase (UniProtKB) and International Protein Index (IPI). It is a central dataset for other major multi-species databases, such as Ensembl and NCBI. Because of the multi-species nature of the UniProtKB, UniProtKB-GOA assists in the curation of 200,000 species. This involves electronic annotation and the integration of high-quality manual GO annotation from all GO Consortium model organism groups and specialist groups. Gene Association Files can be accessed from the Downloads section of the website.
View all literature mentionsSoftware package for functional analysis of sequences by classifying them into families and predicting presence of domains and sites. Scans sequences against InterPro's signatures. Characterizes nucleotide or protein function by matching it with models from several different databases. Used in large scale analysis of whole proteomes, genomes and metagenomes. Available as Web based version and standalone Perl version and SOAP Web Service.
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View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsSoftware for cluster analysis of microarray data. Genesis is a platform independent Java package of tools to simultaneously visualize and analyze a whole set of gene expression experiments.
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
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