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When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases
Dalila Boi1, Elisabetta Rubini1, Sara Breccia1
1Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Abstract:
Myc transcription factors are key regulators of many cellular processes, with Myc target genes crucially implicated in the management of cell proliferation and stem pluripotency, energy metabolism, protein synthesis, angiogenesis, DNA damage response, and apoptosis. Given the wide involvement of Myc in cellular dynamics, it is not surprising that its overexpression is frequently associated with cancer. Noteworthy, in cancer cells where high Myc levels are maintained, the overexpression of Myc-associated kinases is often observed and required to foster tumour cells' proliferation. A mutual interplay exists between Myc and kinases: the latter, which are Myc transcriptional targets, phosphorylate Myc, allowing its transcriptional activity, highlighting a clear regulatory loop. At the protein level, Myc activity and turnover is also tightly regulated by kinases, with a finely tuned balance between translation and rapid protein degradation. In this perspective, we focus on the cross-regulation of Myc and its associated protein kinases underlying similar and redundant mechanisms of regulation at different levels, from transcriptional to post-translational events. Furthermore, a review of the indirect effects of known kinase inhibitors on Myc provides an opportunity to identify alternative and combined therapeutic approaches for cancer treatment.
Insights
Myc transcription factors regulate cell processes, and their overexpression drives cancer. Kinases interact with Myc, controlling its activity and turnover, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- Myc transcription factors are crucial regulators of cell proliferation, stem cell pluripotency, metabolism, and apoptosis.
- Myc overexpression is frequently observed in various cancers, driving tumor cell proliferation.
- Myc and associated kinases exhibit a mutual regulatory interplay, influencing transcriptional activity and protein turnover.
Purpose of the Study:
- To explore the cross-regulation between Myc and its associated protein kinases.
- To elucidate the mechanisms underlying Myc and kinase interactions at transcriptional and post-translational levels.
- To identify potential therapeutic strategies by reviewing the indirect effects of kinase inhibitors on Myc.
Main Methods:
- Literature review focusing on the interplay between Myc and kinases.
- Analysis of transcriptional and post-translational regulatory mechanisms.
- Examination of existing kinase inhibitor data for indirect effects on Myc.
Main Results:
- Myc and kinases form a regulatory loop, with kinases phosphorylating Myc to modulate its activity.
- Kinases tightly control Myc protein levels through a balance of translation and degradation.
- Kinase inhibitors show indirect effects on Myc, suggesting potential for combined cancer therapies.
Conclusions:
- The intricate cross-regulation between Myc and kinases offers insights into cancer development.
- Targeting this Myc-kinase axis presents a promising avenue for novel cancer therapeutics.
- Understanding these interactions can lead to the development of combined therapeutic approaches for cancer treatment.
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