The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Bax Loss Impairs Myc-Induced Apoptosis and Circumvents the Selection of p53 Mutations during Myc-Mediated Lymphomagenesis
Open accessAbstract
The ARF and p53 tumor suppressors mediate Myc-induced apoptosis and suppress lymphoma development in E mu-myc transgenic mice. Here we report that the proapoptotic Bcl-2 family member Bax also mediates apoptosis triggered by Myc and inhibits Myc-induced lymphomagenesis. Bax-deficient primary pre-B cells are resistant to the apoptotic effects of Myc, and Bax loss accelerates lymphoma development in E mu-myc transgenics in a dose-dependent fashion. Eighty percent of lymphomas arising in wild-type E mu-myc transgenics have alterations in the ARF-Mdm2-p53 tumor suppressor pathway characterized by deletions in ARF, mutations or deletions of p53, and overexpression of Mdm2. The absence of Bax did not alter the frequency of biallelic deletion of ARF in lymphomas arising in E mu-myc transgenic mice or the rate of tumorigenesis in ARF-null mice. Furthermore, Mdm2 was overexpressed at the same frequency in lymphomas irrespective of Bax status, suggesting that Bax resides in a pathway separate from ARF and Mdm2. Strikingly, lymphomas from Bax-null E mu-myc transgenics lacked p53 alterations, whereas 27% of the tumors in Bax(+/-) E mu-myc transgenic mice contained p53 mutations or deletions. Thus, the loss of Bax eliminates the selection of p53 mutations and deletions, but not ARF deletions or Mdm2 overexpression, during Myc-induced tumorigenesis, formally demonstrating that Myc-induced apoptotic signals through ARF/Mdm2 and p53 must bifurcate: p53 signals through Bax, whereas this is not necessarily the case for ARF and Mdm2.
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Cites
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Self-citationMyc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
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Cited by
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219
Reprogramming of human somatic cells to pluripotency with defined factors
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Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
Singh, R., Letai, A., & Sarosiek, K. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0089-8 · Cited by 2,111
Reflecting on 25 years with MYC
Meyer, N., & Penn, L. Z. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2231 · Cited by 1,575
Fridman, J. S., & Lowe, S. W. (2003) · Oncogene · doi:10.1038/sj.onc.1207116 · Cited by 1,401
Metadata
- Authors
- Eischen, C. M., Roussel, M. F., Korsmeyer, S. J., & Cleveland, J. L.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-11-01
- Volume
- 21
- Issue
- 22
- Pages
- 7653-7662
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2154813909
- Cited by
- 183
- References
- 13
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- green
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- Eischen, C. M., Roussel, M. F., Korsmeyer, S. J., & Cleveland, J. L. (2001). Bax Loss Impairs Myc-Induced Apoptosis and Circumvents the Selection of p53 Mutations during Myc-Mediated Lymphomagenesis. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.21.22.7653-7662.2001
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