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PMID: 8756660 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Inhibition of c-myc expression induces apoptosis of WEHI 231 murine B cells.

Molecular and cellular biology ·Vol. 16 ·No. 9 ·1996-09-00 ·Pages 5015-25

Wu M, Arsura M, Bellas RE, FitzGerald MJ, Lee H, Schauer SL, Sherr DH, Sonenshein GE

Abstract

Treatment of WEHI 231 immature B-lymphoma cells with an antibody against their surface immunoglobulin (anti-Ig) induces apoptosis and has been studied extensively as a model of B-cell tolerance. Anti-Ig treatment of exponentially growing WEHI 231 cells results in an early transient increase in c-myc expression that is followed by a decline to below basal levels; this decrease in c-myc expression immediately precedes the induction of cell death. Here we have modulated NF-kappaB/Rel factor activity, which regulates the rate of c-myc gene transcription, to determine whether the increase or decrease in c-Myc-levels mediates apoptosis in WEHI 231 cells. Addition of the serine/threonine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), which blocks the normally rapid turnover of the specific inhibitor of NF-kappaB/Rel IkappaBalpha in these cells, caused a drop in Rel-related factor binding. TPCK treatment resulted in decreased c-myc expression, preventing the usual increase seen following anti-Ig treatment. Whereas inhibition of the induction of c-myc expression mediated by anti-Ig failed to block apoptosis, reduction of c-myc expression in exponentially growing WEHI 231 cells induced apoptosis even in the absence of anti-Ig treatment. In WEHI 231 clones ectopically expressing c-Myc, apoptosis induced by treatment with TPCK or anti-Ig was significantly diminished and cells continued to proliferate. Furthermore, apoptosis of WEHI 231 cells ensued following enhanced expression of Mad1, which has been found to reduce functional c-Myc levels. These results indicate that the decline in c-myc expression resulting from the drop in NF-kappaB/Rel binding leads to activation of apoptosis of WEHI 231 B cells.

MeSH Terms
Animals Apoptosis/drug effects,genetics B-Lymphocytes/drug effects,metabolism Carrier Proteins Cell Cycle Proteins Cytomegalovirus/genetics Gene Expression Regulation, Neoplastic/drug effects Humans Lymphoma, B-Cell/pathology Mice NF-kappa B/metabolism Neoplasm Proteins/biosynthesis,genetics Nuclear Proteins/genetics Phosphoproteins/genetics Protein Binding/drug effects Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-myc/biosynthesis,genetics Proto-Oncogene Proteins c-rel Recombinant Fusion Proteins/metabolism Repressor Proteins Tosylphenylalanyl Chloromethyl Ketone/pharmacology Transcription Factors/metabolism Tumor Cells, Cultured/drug effects
Chemicals
Carrier Proteins Cell Cycle Proteins MAD1L1 protein, human Mad1l1 protein, mouse NF-kappa B Neoplasm Proteins Nuclear Proteins Phosphoproteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc Proto-Oncogene Proteins c-rel Recombinant Fusion Proteins Repressor Proteins Transcription Factors Tosylphenylalanyl Chloromethyl Ketone
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wu M
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
Arsura M
Bellas R E
FitzGerald M J
Lee H
Schauer S L
Sherr D H
Sonenshein G E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.9.5015
Published
1996-09-00
Pages
5015-25
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231503
Subset
IM
Grants
NIEHS NIH HHS · 1P4ES07381 · United States
NCI NIH HHS · CA36355 · United States
NIEHS NIH HHS · ES06086 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.9.5015 PMC Full Text View journal details
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