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bioRxiv · 10.1101/556522

Max deletion destabilizes MYC protein and abrogates Eμ-Myc lymphomagenesis

Mathsyaraja, H.·Freie, B.·Cheng, P.-F.·Babaeva, E.·Janssens, D.·Henikoff, S.·Eisenman, R. N.
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Abstract

Although MAX is widely regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is not well defined. We show that B-cell specific deletion of Max has a surprisingly modest effect on B-cell development but completely abrogates E{micro}-Myc driven lymphomagenesis. In both contexts, MAX loss leads to a significant reduction in MYC protein levels. This outcome is associated with the downregulation of numerous transcriptional targets of MAX including a subset that regulate MYC stability. Reduction in MYC protein levels is also observed in multiple cell lines treated with a MYC-MAX dimerization inhibitor. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal lymphoid development.

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Mathsyaraja, H., Freie, B., Cheng, P.-F., Babaeva, E., Janssens, D., Henikoff, S., Eisenman, R. N.. 2019-02-21. Max deletion destabilizes MYC protein and abrogates Eμ-Myc lymphomagenesis. https://doi.org/10.1101/556522

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