期刊
GENES
卷 8, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/genes8070174
关键词
cancer; oncogenes; tumor suppressor genes; cell cycle; cellular senescence; transcription; phosphorylation; post-translational modifications; the ubiquitin/proteasome system; protein-protein interactions
资金
- Swedish Cancer Society
- Swedish Childhood Cancer Foundation
- Swedish Research Council
- Knut and Alice Wallenberg Foundations
- Olle Engkvists Foundation
- Karolinska Institutet Foundations
- Lars Hierta Memorial Foundation
- Foundation of the Langman Cultural Foundation
- Felix Mindus Leukemia Research Grant
- Mary Beves Childhood Cancer Research Grant
MYC is a pleiotropic transcription factor that controls a number of fundamental cellular processes required for the proliferation and survival of normal and malignant cells, including the cell cycle. MYC interacts with several central cell cycle regulators that control the balance between cell cycle progression and temporary or permanent cell cycle arrest (cellular senescence). Among these are the cyclin E/A/cyclin-dependent kinase 2 (CDK2) complexes, the CDK inhibitor p27(KIP1) (p27) and the E3 ubiquitin ligase component S-phase kinase-associated protein 2 (SKP2), which control each other by forming a triangular network. MYC is engaged in bidirectional crosstalk with each of these players; while MYC regulates their expression and/or activity, these factors in turn modulate MYC through protein interactions and post-translational modifications including phosphorylation and ubiquitylation, impacting on MYC's transcriptional output on genes involved in cell cycle progression and senescence. Here we elaborate on these network interactions with MYC and their impact on transcription, cell cycle, replication and stress signaling, and on the role of other players interconnected to this network, such as CDK1, the retinoblastoma protein (pRB), protein phosphatase 2A (PP2A), the F-box proteins FBXW7 and FBXO28, the RAS oncoprotein and the ubiquitin/proteasome system. Finally, we describe how the MYC/CDK2/p27/SKP2 axis impacts on tumor development and discuss possible ways to interfere therapeutically with this system to improve cancer treatment.
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