p19ARF directly and differentially controls the functions of c-Myc independently of p53

Ying Qi, Mark A. Gregory, Zhaoliang Li, Jeffrey P. Brousal, Kimberly West and Stephen R. Hann ()
Additional contact information
Ying Qi: Vanderbilt University School of Medicine
Mark A. Gregory: Vanderbilt University School of Medicine
Zhaoliang Li: Vanderbilt University School of Medicine
Jeffrey P. Brousal: Vanderbilt University School of Medicine
Kimberly West: Vanderbilt University School of Medicine
Stephen R. Hann: Vanderbilt University School of Medicine

Nature, 2004, vol. 431, issue 7009, 712-717

Abstract: Abstract Increased expression of the oncogenic transcription factor c-Myc causes unregulated cell cycle progression1. c-Myc can also cause apoptosis, but it is not known whether the activation and/or repression of c-Myc target genes mediates these diverse functions of c-Myc. Because unchecked cell cycle progression leads to hyperproliferation and tumorigenesis, it is essential for tumour suppressors, such as p53 and p19ARF (ARF), to curb cell cycle progression in response to increased c-Myc (refs 2, 3). Increased c-Myc has previously been shown to induce ARF expression, which leads to cell cycle arrest or apoptosis through the activation of p53 (ref. 4). Here we show that ARF can inhibit c-Myc by a unique and direct mechanism that is independent of p53. When c-Myc increases, ARF binds with c-Myc and dramatically blocks c-Myc's ability to activate transcription and induce hyperproliferation and transformation. In contrast, c-Myc's ability to repress transcription is unaffected by ARF and c-Myc-mediated apoptosis is enhanced. These differential effects of ARF on c-Myc function suggest that separate molecular mechanisms mediate c-Myc-induced hyperproliferation and apoptosis. This direct feedback mechanism represents a p53-independent checkpoint to prevent c-Myc-mediated tumorigenesis.

Date: 2004
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature02958 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:431:y:2004:i:7009:d:10.1038_nature02958

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

DOI: 10.1038/nature02958

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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