PXD033637

PXD033637 is an original dataset announced via ProteomeXchange.

Title	PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins
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.
HostingRepository	PRIDE
AnnounceDate	2024-02-03
AnnouncementXML	Submission_2024-02-03_10:20:09.317.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qimei Pan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; phosphorylated residue
Instrument	Thermo Scientific instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-04 14:37:41	ID requested
⏵ 1	2024-02-03 10:20:09	announced

10.1083/JCB.202308066;

submitter keyword: PC4, PTM, cell cycle, RBP

Chunmeng Shi
contact affiliation	Third Military Medical University(Army Medical University)
contact email	shicm@tmmu.edu.cn
lab head
Qimei Pan
contact affiliation	Army Medical University
contact email	mayble_pan@sina.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033637
     1. Label: PRIDE project
     2. Name: PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins