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. 2024 Feb 13;223(3):e202308066. doi: 10.1083/jcb.202308066

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© 2024 Pan et al.

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Figure 8. — PC4 modifications regulate the dynamic of CCND1 mRNA stability across the cell cycle. Model summarizing: PC4 plays a posttranscriptional regulatory role in controlling the stability of CCND1 mRNA during the cell cycle. The modifications of PC4 undergo periodic changes and they regulate the fluctuations in CCND1 mRNA stability. In interphase, PC4 interacts with TRIM28 and is ubiquitinated (Ub) at residue K68 by TRIM28. This ubiquitination enhances PC4’s binding affinity with CCND1 mRNA, leading to increased stability and protein expression of CCND1. This promotes the transition from G1 to S phase. On the other hand, during mitosis, PC4 is phosphorylated at residue S17 by CK2. This phosphorylation inhibits PC4’s interaction with TRIM28, preventing K68 ubiquitination and impairing PC4’s binding to CCND1 mRNA. Consequently, the degradation of CCND1 mRNA increases.