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Updated: Aug 7, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
The intricacies of p21 phosphorylation: protein/protein interactions, subcellular localization and stability
1Division of Cell & Molecular Biology, Faculty of Natural Sciences, Imperial College London, South Kensington, London, UK. emma.child@imperial.ac.uk
Abstract:
p21 was originally described as functioning as a cell cycle regulator via inhibition of both cyclin-dependent kinases and processive DNA replication. Nowadays it is recognized to play other fundamental roles including transcriptional regulation and the modulation of apoptosis. Each of these functions of p21 is achieved through direct p21/protein interactions and the subcellular localization of p21 plays an important part in dictating the binding partners to which p21 is exposed. Over recent years, a number of phosphorylation sites in p21 have been identified, these being targeted by several important intracellular signalling protein kinases. Here we review the state of our knowledge of p21 phosphorylation with respect to the kinases involved and the molecular biological effects of each phosphorylation event.
Insights
The protein p21, initially a cell cycle regulator, also modulates apoptosis and transcription. Its functions are dictated by protein interactions and location, influenced by phosphorylation events from various kinases.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The protein p21 (cyclin-dependent kinase inhibitor 1) was initially identified for its role in cell cycle regulation.
- Emerging evidence highlights p21's involvement in diverse cellular processes, including transcriptional regulation and apoptosis.
- p21's functions are critically dependent on its interactions with other proteins, which are influenced by its subcellular localization.
Purpose of the Study:
- To review the current understanding of p21 phosphorylation.
- To identify the specific kinases that phosphorylate p21.
- To elucidate the molecular consequences of p21 phosphorylation events.
Main Methods:
- Literature review of studies on p21 phosphorylation.
- Analysis of identified p21 phosphorylation sites.
- Examination of the kinases involved in p21 phosphorylation.
- Assessment of the downstream molecular effects of p21 phosphorylation.
Main Results:
- Multiple phosphorylation sites on p21 have been identified.
- Several intracellular signaling protein kinases target these p21 phosphorylation sites.
- Phosphorylation influences p21's interactions and subcellular localization, thereby modulating its diverse functions.
Conclusions:
- p21 phosphorylation is a key regulatory mechanism controlling its multifaceted roles beyond cell cycle inhibition.
- Understanding p21 phosphorylation provides insights into its regulation of transcription and apoptosis.
- Further research into p21 phosphorylation is crucial for fully elucidating its biological significance.
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