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Genes 2017, 8(7), 174; doi:10.3390/genes8070174

MYC Modulation around the CDK2/p27/SKP2 Axis

1
Department of Oncology-Pathology, Karolinska Institutet, SE-171 76 Stockholm, Sweden
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Daitoku Sakamuro
Received: 29 May 2017 / Revised: 23 June 2017 / Accepted: 24 June 2017 / Published: 30 June 2017
(This article belongs to the Special Issue MYC Networks)
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Abstract

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 p27KIP1 (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. View Full-Text
Keywords: cancer; oncogenes; tumor suppressor genes; cell cycle; cellular senescence; transcription; phosphorylation; post-translational modifications; the ubiquitin/proteasome system; protein–protein interactions cancer; oncogenes; tumor suppressor genes; cell cycle; cellular senescence; transcription; phosphorylation; post-translational modifications; the ubiquitin/proteasome system; protein–protein interactions
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hydbring, P.; Castell, A.; Larsson, L.-G. MYC Modulation around the CDK2/p27/SKP2 Axis. Genes 2017, 8, 174.

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