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Updated: May 22, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
RNA processing and modification protein, carbon catabolite repression 4 (Ccr4), arrests the cell cycle through
1Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
Abstract:
Ccr4d is a new member of the Ccr4 (carbon catabolite repression 4) family of proteins that are implicated in the regulation of mRNA stability and translation through mRNA deadenylation. However, Ccr4d is not believed to be involved in mRNA deadenylation. Thus, its biological function and mechanistic activity remain to be determined. Here, we report that Ccr4d is broadly expressed in various normal tissues, and the expression of Ccr4d is markedly down-regulated during cell cycle progression. We showed that Ccr4d inhibits cell proliferation and induces cell cycle arrest at G(1) phase. Our experiments further revealed that Ccr4d regulates the expression of p21 in a p53-independent manner. Mechanistic studies indicated that Ccr4d strongly bound to the 3'-UTR of p21 mRNA, leading to the stabilization of p21 mRNA. Interestingly, we found that the expression of Ccr4d is down-regulated in various tumor tissues. Collectively, our data indicate that Ccr4d functions as an anti-proliferating protein through the induction of cell cycle arrest via a p21-dependent and p53-independent pathway and suggest that Ccr4d might have an important role in carcinogenesis.
Insights
Carbon catabolite repression 4 domain containing (Ccr4d) protein inhibits cell proliferation by arresting the cell cycle at G1 phase. Ccr4d also stabilizes p21 mRNA, suggesting a role in preventing cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The Ccr4 (carbon catabolite repression 4) family regulates mRNA stability and translation.
- Ccr4d, a novel member, is not involved in mRNA deadenylation, necessitating functional investigation.
Purpose of the Study:
- To determine the biological function and mechanism of Ccr4d.
- To investigate Ccr4d's role in cell proliferation and cell cycle regulation.
- To explore Ccr4d's potential involvement in carcinogenesis.
Main Methods:
- Analysis of Ccr4d expression in normal and tumor tissues.
- Cell proliferation assays and cell cycle analysis (G1 arrest).
- Investigation of Ccr4d's effect on p21 expression and p53-independent pathways.
- RNA-binding studies focusing on the 3'-UTR of p21 mRNA.
Main Results:
- Ccr4d is broadly expressed in normal tissues but down-regulated in tumors.
- Ccr4d inhibits cell proliferation and induces G1 cell cycle arrest.
- Ccr4d stabilizes p21 mRNA through binding to its 3'-UTR in a p53-independent manner.
Conclusions:
- Ccr4d acts as an anti-proliferative protein by inducing cell cycle arrest via a p21-dependent pathway.
- Down-regulation of Ccr4d in tumors suggests its role as a tumor suppressor.
- Ccr4d may play a significant role in preventing carcinogenesis.
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