Oncogenic PKA signaling stabilizes MYC oncoproteins via an aurora kinase A-dependent mechanism

Chan, Gary KL; Maisel, Samantha; Hwang, Yeonjoo; Rrb, Wolber; P, Vu; Kc, Patra; Bouhaddou, Mehdi; Hl, Kenerson; Rs, Yeung; Dl, Swaney; Nj, Krogan; Re, Turnham; Jd, Scott; Riehle, KJ; Bardeesy, Nabeel; Jd, Gordan

doi:10.1101/2021.04.16.438110

Cited by 1 publication

(2 citation statements)

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“…Additionally, among PKACα (but not PKACβ) substrates, ENO1 and MBP1, which are splice variants described as Myc transcriptional repressors, have gained attention [85]. Some studies have observed increased levels of c-and N-Myc in cAMP stimulation conditions, while PKACα siRNA attenuates phosphorylation of its substrates and progressively decreases c-and N-Myc protein levels [55].…”

Section: Pkamentioning

confidence: 99%

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When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases

Boi

Rubini

Breccia

et al. 2023

IJMS

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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.

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Section: Pkamentioning

confidence: 99%

“…The cell-cycle-dependent Aurora-A and Aurora-B form a circuit with Myc, in which Aurora primes the oncogenic program of Myc and vice versa [53,54]. Aurora-A is also involved in Myc modulation in PKA-dependent tumours [55]. Other kinases are crucial for Myc transcriptional activity (i.e., PIM and BRD4 [56][57][58]).…”

Section: Introductionmentioning

confidence: 99%