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PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE202401 | GEO | 2024/02/11

REPOSITORIES: GEO

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PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

Project description:The cell cycle is an intensively control process, in which cell-cycle proteins display a cyclical expression pattern regulated by specific transcription, translation and degradation. Cell cycle progression is initiated by highly expressed D-type cyclins (D1/2/3) to facilitate DNA synthesis, subsequently driven by mitotic proteins formation (e.g., centromere proteins) that is responsible for mitosis onset. Whether there exist master regulators to keep the cycle rapidly “running” with D-type cyclins induction, as well as maintain the cycle in a stable process by centromere proteins modulation is of particular interest yet remains unclear at present. Here our study clarifies human positive cofactor 4 (PC4) as a previously unrecognized RNA binding protein (RBP), as a post-transcriptional master regulator to orchestrate CCND1 and CENPF expression. We reveal that lack of PC4 reduces CCND1 stability whereas enhances excessive CENPF translation, results in cell cycle arrest and mitotic defects. Furthermore, PC4 RNA binding activity is strictly controlled by S17 phosphorylation and K68 ubiquitination in a cell cycle-dependent way. Lastly, we use in vivo model to verify that PC4 deficiency amplifies response of cancer cells to CDK4/6 inhibitor, and PC4 induction accelerates liver regeneration after partial hepatectomy. These results highlight that cell-cycle gene expressions are dynamically and post-transcriptionally fine-tuned, and identify PC4 as an essential cell-cycle post-transcriptional manipulator that is profoundly applied within cancer and regeneration medicine.

2024-02-03 | PXD033637 | Pride

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (eCLIP-Seq).

Project description:To investigate the binding site in which PC4 protein association with its target RNAs. eCLIP-seq was performed to profile PC4-binding RNA targets in Huh7 cells.

2024-02-12 | GSE202400 | GEO

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RIP-Seq).

Project description:To investigate the mRNA targets of PC4 that worked as an RNA binding protein to control cell cycle progression. RIP-seq was displayed to profile PC4-binding RNA targets in Huh7 cells.

2024-02-12 | GSE202399 | GEO

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RNA-Seq).

Project description:To investigate the downstream targets of PC4 in controlling cell cycle, we knockdowned PC4 with two different siRNAs in Huh7 cells. We performed RNA-seq in Huh7 cells transfected with NC, siPC4-1 or siPC4-2.

2024-02-12 | GSE202397 | GEO

Post-Transcriptional Regulation of Mouse Neurogenesis by Pumilio Proteins

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