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P27 binds to promoters of multiple genes leading to their repression

ABSTRACT: The role of the cyclin-cdk inhibitor p27 in tumorigenesis is still a controversial matter. We demonstrate here that p27 negatively regulates transcription of a number of genes (p27-target genes) involved in key cellular functions as RNA processing, translation, respiration and cell proliferation.

ORGANISM(S): Mus musculus

PROVIDER: GSE20068 | GEO | 2011/12/01

SECONDARY ACCESSION(S): PRJNA129795

REPOSITORIES: GEO

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p27 binds to promoters of multiple genes leading to their repression

Project description:The role of the cyclin-cdk inhibitor p27 in tumorigenesis is still a controversial matter. We demonstrate here that p27 negatively regulates transcription of a number of genes (p27-target genes) involved in key cellular functions as RNA processing, translation, respiration and cell proliferation. Crosslinked chromatin from quiescent NIH3T3 cells was sonicated, incubated overnight with the rabbit anti-p27 and IgG antibodies as control

2011-12-01 | E-GEOD-20068 | biostudies-arrayexpress

C-terminally phosphorylated p27 regulates STAT3 transcriptional activation, inducing gene programs driving mammary duct and cancer stem cell expansion

Project description:While, p27 inhibits cell cycle in normal cells, in most cancers, p27 acquires oncogenic activities when phosphorylated by PI3K-activated kinases at T157 and T198 (p27pTpT). Mechanistically, these oncogenic functions of p27pTpT are poorly understood. Here, we show that p27pTpT promotes cancer stem cell (CSC) expansion through STAT3 both in vitro and in vivo. p27 phosphorylation increased STAT3 recruitment to chromatin to induce CSC self-renewal genes including MYC, the Notch ligand, JAG1, and ANGPTL4. We identify a feed-forward loop in which p27pTpT/STAT3 co-represses the Pyk2 inhibitor, PTPN12. Pyk2 in turn activates STAT3, driving CSCs expansion. p27pTpT is also shown to critically regulate mammary gland development. Mammary transgenic expression of phosphomimetic, cyclin-CDK binding defective p27 (p27CK-DD) increases mammary duct branching morphogenesis and hyperplasia, yielding primary and metastatic breast cancers. This supports a model in which p27pTpT co-regulates STAT3 to drive programs governing stem cell expansion or maintenance in normal and cancer tissues.

2024-04-19 | GSE233351 | GEO

p27-affinity-purified mass spectrometry anslysis

Project description:This project aims to identify p27 modification sites.

2023-01-05 | PXD039223 | Pride

Rhodococcus sp. P27

Project description:Rhodococcus sp. P27 Genome sequencing and assembly

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Cisplatin induces the rearrangement of RBPs on CDKN1B/p27 mRNA

Project description:Cisplatin (CP) is a chemotherapeutic drug that is used to cure different types of cancer. CP induces DNA damage and leads to cell cycle arrest. The cyclin-dependent kinase inhibitor 1B (CDKN1B), also termed p27, plays an important role in the drug response ; and increased levels of p27 correlated with CP resistance. In HEK293 cells, we observed that p27 mRNAs levels increased whereas protein level drastically decreased in cells treated with CP; suggesting post-transcriptional regulatory events. To further understand the underlying mechanisms, we applied a biochemical approach combined with mass-spectrometry to systematically identify the RNA-binding proteins (RBPs) that are bound to the 3’UTR of p27 mRNAs in CP-treated versus non-treated cells in vivo. We found that 24 proteins, most of them known RBPs such HuR, hNRNPD, changed their association with p27 mRNA upon CP treatement. Furthermore, knock-down of a subset of the identified RBPs led to the inhibition of the CP-induced increase of p27 mRNA levels. In conclusion, these results highlight substantial rearrangement between RBPs and p27 mRNA upon CP treatment and corroborate the importance of post-transcriptional control in cellular drug response.

2019-09-27 | PXD008498 | Pride

Genome-wide profile of cJun and p27 in breast cancer cells

Project description:We report the genome-wide profile of cJun and p27 in _231 (a line selected for low metastatic ability), _231-1833 (its bone-tropic metastatic derivative line), _231p27CK-DD (a phosphomimetic cell line), and _231-1833shp27 (p27 knockdown cell line). It shows that cJun and p27 broadly binds to genomic DNA and their bindings are regulated by p27 phosphorylation-dependent patterns.

2019-03-19 | GSE112444 | GEO

BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein

Project description:Coordinated BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. Persistence of oncogenic p27 functions despite effective inhibition of BCR-ABL1 may contribute to resistance to tyrosine kinase inhibitors. BCR-ABL1 induced p27 versus knockout, controlling with Empty vector p27 versus knock out

2014-10-08 | E-GEOD-59168 | biostudies-arrayexpress

Caffeine-regulated transcripts in mouse hearts are p27-dependent

Project description:Overall question: How does caffeine administration for 10 days with the drinking water change the transcriptome of the heart? Are these changes dependent on the protein p27? Results: 242 of the 245 transcripts differentially regulated after caffeine administration in wildtype animals are p27 dependent, since they are not changed in p27-deficient littermates. Among the most highly enriched gene ontology (GO) categories for biological processes are GO-terms describing pathways, which take place in the mitochondria.

2017-11-30 | GSE100489 | GEO

BCR-ABL1 promotes leukemia by converting p27 into a cytoplasmic oncoprotein

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Distribution of p27- and PCAF binding sites (BS) on the chromatin of HCT116 cell line

Project description:We analyzed the transcriptional programs regulated by PCAF and p27 in the colon cancer cell line HCT116 by ChIP-seq. We identified 269 protein-encoding genes that contain both p27 and PCAF binding sites being the majority of these sites different for PCAF and p27

2017-06-10 | GSE93975 | GEO

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