MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor–1

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 8, 2021

The oncoprotein transcription factor MYC is a major driver of malignancy and highly validated but challenging target for the development anticancer therapies. Novel strategies to inhibit may come from understanding co-factors it uses drive pro-tumorigenic gene expression programs, providing their role in activity understood. Here we interrogate how one co-factor, host cell (HCF)–1, contributes human Burkitt lymphoma setting. We identify genes connected mitochondrial function ribosome biogenesis as direct MYC/HCF-1 targets demonstrate modulation MYC–HCF-1 interaction influences growth, metabolite profiles, global patterns, tumor growth vivo. This work defines HCF-1 critical places biological context, highlights focal point novel anti-MYC

Language: Английский

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Targeting MYCN in Pediatric and Adult Cancers

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 10

Published: Feb. 8, 2021

The deregulation of the MYC family oncogenes, including c-MYC, MYCN and MYCL occurs in many types cancers, is frequently associated with a poor prognosis. majority functional studies have focused on c-MYC due to its broad expression profile human cancers. existence highly conserved domains between suggests that participates similar activities. encodes basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (TF) whose central oncogenic role cancers makes it desirable therapeutic target. Historically, as TF, has been regarded "undruggable". Thus, recent efforts focus investigating methods indirectly target achieve anti-tumor effects. This review will primarily summarize progress understanding function MYCN. It explore at targeting MYCN, strategies aimed suppression transcription, destabilization protein, inhibition transcriptional activity, repression targets utilization overexpression dependent synthetic lethality.

Language: Английский

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MYC assembles and stimulates topoisomerases 1 and 2 in a “topoisome”

Molecular Cell, Journal Year: 2021, Volume and Issue: 82(1), P. 140 - 158.e12

Published: Dec. 9, 2021

High-intensity transcription and replication supercoil DNA to levels that can impede or halt these processes. As a potent amplifier accelerator, the proto-oncogene MYC must manage this interfering torsional stress. By comparing gene expression with recruitment of topoisomerases promoters, we surmised direct association topoisomerase 1 (TOP1) TOP2 was confirmed in vitro cells. Beyond recruiting topoisomerases, directly stimulates their activities. We identify MYC-nucleated "topoisome" complex unites TOP1 increases activities at bodies, enhancers. Whether TOP2A TOP2B is included topoisome dictated by presence versus MYCN, respectively. Thus, cells, assembles tools simplify topology promote genome function under high output conditions.

Language: Английский

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Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(9), P. 1864 - 1873

Published: March 16, 2022

Language: Английский

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MYC multimers shield stalled replication forks from RNA polymerase

Nature, Journal Year: 2022, Volume and Issue: 612(7938), P. 148 - 155

Published: Nov. 23, 2022

Language: Английский

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