Inhibition of c-<i>myc</i> Expression Induces Apoptosis of WEHI 231 Murine B Cells

Wu, Min; Arsura, Marcello; Bellas, Robert E.; FitzGerald, Mark; Lee, H; Schauer, Stephanie L.; Sherr, David H.; Sonenshein, Gail E.

doi:10.1128/mcb.16.9.5015

Cited by 133 publications

(121 citation statements)

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“…16,17 In B lymphocytes, downmodulation of c-myc expression correlates with induction of apoptosis in B-cell lines. [18][19][20] Anti-CD40 stimulation of B lymphocytes induces the surface expression of CD95 and makes them susceptible to cell death by this receptor. [21][22][23] Furthermore, addition of interleukin 4 to anti-CD40-activated B lymphocytes renders these cells more resistant to CD95-induced cell death.…”

Section: Introductionmentioning

confidence: 99%

c-Myc-deficient B lymphocytes are resistant to spontaneous and induced cell death

2003

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C-myc gene is a member of the myc family of protooncogenes involved in proliferation, differentiation, and apoptosis. Overexpression of c-myc in fibroblasts causes apoptosis under low serum conditions in a process that requires the interaction of CD95 and CD95L on the surface. We have previously reported an in vivo conditional model to inactivate the c-myc gene in B lymphocytes. Here, we show that c-Myc-deficient primary B lymphocytes are resistant to different apoptotic stimuli. Nonactivated c-Myc-deficient B cells are resistant to spontaneous cell death. Upon activation, c-Myc-deficient B lymphocytes express normal surface levels of activation markers, and show resistance to staurosporine and CD95-induced cell death.

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Section: Introductionmentioning

confidence: 99%

c-Myc-deficient B lymphocytes are resistant to spontaneous and induced cell death

2003

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“…The strongest experimental evidence that supports this notion is that overexpression of exogenous c-Myc protects WEHI-231 cells from anti-IgM-induced apoptosis [45] and that stabilization of c-Myc levels by antisense c-myc oligodeoxynucleotides rescues WEHI-231 and CH31 cells from antiIgM-induced apoptosis [40]. Conversely, inhibition of c-Myc expression using a serine/ threonine protease inhibitor TPCK (N-tosyl-L-phenylalanine chloromethyl ketone) induces apoptosis in WEHI-231 cells [45]. Additionally, down-regulation of c-Myc (using a pharmacological inhibitor of c-Myc, FR901228), together with an increase in cytoplasmic free calcium results in accumulation of p27 Kip1 , G1 arrest, and apoptosis in WEHI-231 and ECH408 cells.…”

Section: The Role Of Ras In Bcr Signalingmentioning

confidence: 97%

Activation-induced cell death in B lymphocytes

Donjerković

Scott

2000

Cell Res

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Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activationinduced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLC γ, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.

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“…A comparison of the e ects of N-Myc, L-Myc, and c-Myc in 32D myeloid cells indicates that they di erentially sensitize cells to some stimuli (Nesbit et al, 1998). The literature provides counter examples where under growth limiting conditions c-Myc can promote survival of B lymphocytes (Wu et al, 1996a;Sonenshein, 1997;Wang et al, 1999) or di erentiation of normal human keratinocytes (Gandarillas and Watt, 1997), illustrating the complex cell fate regulating aspects of c-Myc. However, the clear trend in the great majority of cell types examined is for Myc proteins to promote both mitogenesis and cell death under growth limiting conditions.…”

Section: C-myc Induces Apoptosismentioning

confidence: 99%