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Enforced Bcl-2 expression inhibits Myc-induced apoptosis and cooperates with Myc in transformation. Here we report that the synergy between Bcl-2 and Myc in transforming hematopoietic cells in fact reflects a Myc-induced pathway that selectively suppresses the expression of the Bcl-X(L) or Bcl-2 antiapoptotic protein. Myc activation suppresses Bcl-X(L) RNA and protein levels in cultures of primary myeloid and lymphoid progenitors, and Bcl-X(L) and Bcl-2 expression is inhibited by Myc in precancerous B cells from Emu-myc transgenic mice. The suppression of bcl-X RNA levels by Myc requires de novo protein synthesis, indicating that repression is indirect. Importantly, the suppression of Bcl-2 or Bcl-X(L) by Myc is corrupted during Myc-induced tumorigenesis, as Bcl-2 and/or Bcl-X(L) levels are markedly elevated in over one-half of all lymphomas arising in Emicro-myc transgenic mice. Bcl-2 and/or Bcl-X(L) overexpression did not correlate with loss of ARF or p53 function in tumor cells, indicating that these two apoptotic pathways are inactivated independently. Therefore, the suppression of Bcl-X(L) or Bcl-2 expression represents a physiological Myc-induced apoptotic pathway that is frequently bypassed during lymphomagenesis.

Titel:	Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.
Autor/in / Beteiligte Person:	Eischen, CM ; Woo, D ; Roussel, MF ; Cleveland, JL
Link:	Full Text Finder (Volltext)
Zeitschrift:	Molecular and cellular biology, Jg. 21 (2001-08-01), Heft 15, S. 5063-70
Veröffentlichung:	2023- : [Philadelphia] : Taylor & Francis ; <i>Original Publication</i>: [Washington, D.C.] : American Society for Microbiology, [c1981-, 2001
Medientyp:	academicJournal
ISSN:	0270-7306 (print)
DOI:	10.1128/MCB.21.15.5063-5070.2001
Schlagwort:	ADP-Ribosylation Factor 1 metabolism Animals Blotting, Northern Blotting, Western Cell Survival Cells, Cultured Mice Mice, Knockout Mice, Transgenic Myeloid Cells metabolism RNA metabolism Stem Cells metabolism Time Factors Transformation, Genetic Tumor Suppressor Protein p53 metabolism bcl-X Protein Apoptosis Lymph Nodes metabolism Proto-Oncogene Proteins c-bcl-2 metabolism Proto-Oncogene Proteins c-myc metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Language: English [Mol Cell Biol] 2001 Aug; Vol. 21 (15), pp. 5063-70. MeSH Terms: Apoptosis* ; Lymph Nodes / metabolism ; Proto-Oncogene Proteins c-bcl-2 / metabolism ; Proto-Oncogene Proteins c-myc / *metabolism ; ADP-Ribosylation Factor 1 / metabolism ; Animals ; Blotting, Northern ; Blotting, Western ; Cell Survival ; Cells, Cultured ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myeloid Cells / metabolism ; RNA / metabolism ; Stem Cells / metabolism ; Time Factors ; Transformation, Genetic ; Tumor Suppressor Protein p53 / metabolism ; bcl-X Protein References: Biochim Biophys Acta. 1987 Apr 20;907(1):1-32. (PMID: 3552050) ; Genes Dev. 1999 Aug 1;13(15):1899-911. (PMID: 10444588) ; Nature. 1990 Nov 22;348(6299):331-3. (PMID: 2250704) ; Nature. 1991 Jan 17;349(6306):254-6. (PMID: 1987477) ; EMBO J. 1991 Jan;10(1):133-41. 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(PMID: 3258007) Grant Information: R01 DK044158 United States DK NIDDK NIH HHS; CA76379 United States CA NCI NIH HHS; CA81695 United States CA NCI NIH HHS; P01 CA071907 United States CA NCI NIH HHS; DK40700 United States DK NIDDK NIH HHS; CA71907 United States CA NCI NIH HHS; R01 CA076379 United States CA NCI NIH HHS; CA56819 United States CA NCI NIH HHS; CA-21765 United States CA NCI NIH HHS; P30 CA021765 United States CA NCI NIH HHS; DK44158 United States DK NIDDK NIH HHS; F32 CA081695 United States CA NCI NIH HHS; DK45663 United States DK NIDDK NIH HHS Substance Nomenclature: 0 (Bcl2l1 protein, mouse) ; 0 (Proto-Oncogene Proteins c-bcl-2) ; 0 (Proto-Oncogene Proteins c-myc) ; 0 (Tumor Suppressor Protein p53) ; 0 (bcl-X Protein) ; 63231-63-0 (RNA) ; EC 3.6.5.2 (ADP-Ribosylation Factor 1) Entry Date(s): Date Created: 20010705 Date Completed: 20010816 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC87232

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Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.