MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability

Dharmendra Dingar, William B. Tu, Diana Resetca, Corey Lourenco, Aaliya Tamachi, Jason De Melo, Kathleen E. Houlahan, Manpreet Kalkat, Pak-Kei Chan, Paul C. Boutros, Brian Raught and Linda Z. Penn ()
Additional contact information
Dharmendra Dingar: University Health Network
William B. Tu: University Health Network
Diana Resetca: University Health Network
Corey Lourenco: University Health Network
Aaliya Tamachi: University Health Network
Jason De Melo: University Health Network
Kathleen E. Houlahan: University of Toronto
Manpreet Kalkat: University Health Network
Pak-Kei Chan: University Health Network
Paul C. Boutros: University of Toronto
Brian Raught: University Health Network
Linda Z. Penn: University Health Network

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract The c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC interactome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCFFBXW7 pathway. MYC hyperphosphorylation can be rescued specifically with exogenous PP1, but not other phosphatases. Hyperphosphorylated MYC retained interaction with its transcriptional partner MAX, but binding to chromatin is significantly compromised. Our work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05660-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05660-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05660-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().