c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover
10.1182/blood.v95.6.2104
Crossref journal-article
American Society of Hematology
Blood (234)
Abstract

AbstractThe c-myc proto-oncogene encodes a short-lived transcription factor that plays an important role in cell cycle regulation, differentiation and apoptosis. c-myc is often rearranged in tumors resulting in deregulated expression. In addition, mutations in the coding region of c-myc are frequently found in human lymphomas, a hot spot being the Thr58 phosphorylation site, a mutation shown to enhance the transforming capacity of c-Myc. It is, however, still unclear in what way this mutation affects c-Myc activity. Our results show that proteasome-mediated turnover of c-Myc is substantially impaired in Burkitt's lymphoma cells with mutated Thr58 or other mutations that abolish Thr58 phosphorylation, whereas endogenous or ectopically expressed wild type c-Myc proteins turn over at normal rates in these cells. Myc Thr58 mutants expressed ectopically in other cell types also exhibit reduced proteasome-mediated degradation, which correlates with a substantial decrease in their ubiquitination. These results suggest that ubiquitin/proteasome-mediated degradation of c-Myc is triggered by Thr58 phosphorylation revealing a new important level of control of c-Myc activity. Mutation of Thr58 in lymphoma thus escapes this regulation resulting in accumulation of c-Myc protein, likely as part of the tumor progression.

Bibliography

Bahram, F., von der Lehr, N., Cetinkaya, C., & Larsson, L.-G. (2000). c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover. Blood, 95(6), 2104–2110.

Authors 4
  1. Fuad Bahram (first)
  2. Natalie von der Lehr (additional)
  3. Cihan Cetinkaya (additional)
  4. Lars-Gunnar Larsson (additional)
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Dates
Type When
Created 5 years, 10 months ago (Oct. 12, 2019, 4:26 p.m.)
Deposited 4 years, 7 months ago (Jan. 24, 2021, 12:35 p.m.)
Indexed 2 days, 22 hours ago (Aug. 22, 2025, 1:01 a.m.)
Issued 25 years, 5 months ago (March 15, 2000)
Published 25 years, 5 months ago (March 15, 2000)
Published Print 25 years, 5 months ago (March 15, 2000)
Funders 0

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@article{Bahram_2000, title={c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover}, volume={95}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v95.6.2104}, DOI={10.1182/blood.v95.6.2104}, number={6}, journal={Blood}, publisher={American Society of Hematology}, author={Bahram, Fuad and von der Lehr, Natalie and Cetinkaya, Cihan and Larsson, Lars-Gunnar}, year={2000}, month=mar, pages={2104–2110} }