{"database": "metadata", "table": "run_metadata", "rows": [[34690, "SRR32217624", "SRX27557936", "SRS23971737", "SRP561364", "PRJNA1218816", "p21  ccng1  foxo3b and fbxw7 contribute to p53 dependent cell cycle arrest [MPNP timecross]", "GSE288666", "Transcriptome Analysis", "p53 is a transcription factor that plays a critical role in cancer prevention. However  the mechanisms by which p53 exerts its tumor suppressive function is still unclear. While PUMA/BBC3 and NOXA/PMAIP1 are known to be important in p53 dependent apoptosis  and p21/CDKN1A is crucial for p53 dependent cell cycle arrest  we demonstrate that zebrafish lacking puma  noxa  and p21 do not show a predisposition to cancer. This suggests that additional p53 transcriptional targets are sufficient for its tumor suppressive function. Contrary to the prevailing belief that p21 is the key regulator of p53 dependent cell cycle arrest  we provide evidence that p53 can still induce cell cycle arrest in the absence of p21  following DNA damage or loss of mdm2 p53 activation in the absence of stress. This implies the involvement of other p53 transcriptional targets in mediating p53 dependent cell cycle arrest. Since p53 tumor suppression is conserved across multiple vertebrate species  we conducted a cross species comparative analysis of p53 dependent transcriptional profiles to identify a conserved set of 136 p53 upregulated transcripts. Our analysis stresses the importance of ortholog to paralog analysis across species  since in many cases the paralog but not ortholog in differing species is p53 dependent. Additionally  we performed a CRISPR/Cas9 G0 \u201ccrispant\u201d screen in a genetic background lacking mdm2  puma  noxa  and p21 to identify key components involved in p53 dependent cell cycle arrest. Our findings revealed that ccng1  fbxw7  and foxo3b play an important role in this process. Overall design: RNA sequencing was performed on zebrafish of un genotyped progeny from mdm2+/ ; pnp / intercrosses at various developmental stages 8  10  12  14  16 hpf as the mutant group N=50 embryos for each group  referred to as MPNP. While this approach generated a dilution of RNA transcripts  since only approxmiately \u00bc of the embryos were mpnp /   it nonetheless allowed us to glimpse at the dynamics of p53 target gene induction in mpnp /  animals. Same stage progeny from pnp /  intercrosses were harvested to extract RNA for comparison  referred to as PNP.", null, "pubmed:40487439", null, "Zebrafish MPNP 16hpf 2", "GSM8772772", null, "source name:16 hpf embryos|tissue:16 hpf embryos|genotype:mdm2 /  or mdm2+/+  mdm2+/ ; puma / ; noxa / ; p21 / |geo loc name:missing|collection date:missing", "Zebrafish MPNP 16hpf 2", "Raw sequencing reads were aligned to the Danio rerio GRCz11 genome assemblies using STAR version 2.7.3a  GCC 6.4.0 2.28 with default setting. Following alignment  raw read counts were generated using HTSeq version 0.12.3  foss 2018b  Python 3.6.6. The corresponding gene annotation files used in HTSeq were Danio rerio.GRCz11.102.chr.gtf for zebrafish samples. Differentially expressed genes DEGs were identified using DESeq2 version 1.42.1 in R version 4.3.3. Normalized counts were obtained using RSEM version 1.3.3 Assembly: GRCz11 Supplementary files format and content: tab delimited text file includes TPM values for each samples", "16 hpf embryos", null, "Total RNA was extracted using QIAGEN RNeasy Plus Mini Kit QIAGEN  #74134 according to the manufacturer\u2019s instructions. 500 ng of total RNA was used for the construction of sequencing libraries. RNA libraries were prepared using the Illumina RNA kit with PolyA selection. Sequencing was performed on the Illumina HiSeq platform  generating 2x150 bp paired end reads  and was conducted by Genewiz from Azenta Life Sciences.", "The fertilization windown was set to 15 minutes. All embryos were cleaned approximately 6 hpf  with approximately 30 embryos pooled in each Petri dish.", "tissue:16 hpf embryos|genotype:mdm2 /  or mdm2+/+  mdm2+/ ; puma / ; noxa / ; p21 / ", "GSM8772772", "GSM8772772: Zebrafish MPNP 16hpf 2; Danio rerio; RNA Seq", "GSM8772772 r1", "GSM8772772", "1", "Total RNA was extracted using QIAGEN RNeasy Plus Mini Kit QIAGEN  #74134 according to the manufacturer's instructions. 500 ng of total RNA was used for the construction of sequencing libraries. RNA libraries were prepared using the Illumina RNA kit with PolyA selection. Sequencing was performed on the Illumina HiSeq platform  generating 2x150 bp paired end reads  and was conducted by Genewiz from Azenta Life Sciences.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "Illumina HiSeq 2500", null, "SRP561364", null, null, "MPNP-16hpf-R2_R1_001.fastq.gz MPNP-16hpf-R2_R2_001.fastq.gz", "fastq fastq", 14701359300.0, 49004531.0, "GSM8772772 r1", "0:150 1:150", "A:3947459353;C:3409168557;G:3472564779;T:3870403810;N:1762801", 150, 150, null, null, 3947459353, 3409168557, 3472564779, 3870403810, 1762801, "SRX27557936", "SRS23971737", "SRA2069214", "University of Alabama at Birmingham", "University of Alabama at Birmingham", null, null, null, null, null, null, null, null, null, null, null, "B", "B", "biological fallback assumption", "illumina", "hiseq_era", "unknown", "poly_a", "unknown", "bulk", "unknown", "unknown", null, "United States", "2025-02-03", "Multi-stage", "Embryo", "Embryo Imprecise", "All anatomical structures"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["34690"], "units": {}, "query_ms": 11.167931006639265}