Anti-IgM-mediated Regulation of c-myc and Its Possible Relationship to Apoptosis

Kaptein, John S.; Lin, Ching-Kow E.; Wang, C. Linzhi; Nguyen, Tam; Kalunta, Cosmas I.; Park, Eun-Hee; Chen, Fun-Shan; Lad, Pramod M.

doi:10.1074/jbc.271.31.18875

Cited by 50 publications

(30 citation statements)

References 86 publications

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“…In WEHI-231 cells, increases in free calcium levels provide that second signal for growth arrest (32). The dissociation between a decrease in c-Myc and growth arrest in BU-11 cells differs from results obtained with melanoma (37), monomyeloid (38), ovarian carcinoma (39), Burkitt's lymphoma (40), and acute lymphoblastic leukemia (41) cells, in all of which growth arrest is concomitant with a decrease in c-Myc.…”

Section: Figurecontrasting

confidence: 47%

Environmental Chemical-Induced Pro/Pre-B Cell Apoptosis: Analysis of c-Myc, p27Kip1, and p21WAF1 Reveals a Death Pathway Distinct from Clonal Deletion

Ryu

Mann

Schlezinger

et al. 2003

The Journal of Immunology

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Polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that suppress the immune system in part by inducing pro/pre-B cell apoptosis. The PAH-induced death signaling pathway resembles the signaling cascade activated during clonal deletion and modeled by B cell receptor cross-linking or by dexamethasone exposure of immature surface Ig+ B cells in that apoptosis is mediated by NF-κB down-regulation. Because a PAH-induced, clonally nonrestricted deletion of B cells would have important implications for B cell repertoire development, the nature of the PAH-induced intracellular death signal was studied further. Particular emphasis was placed on the roles of growth arrest and c-Myc, p27Kip1, and p21WAF1 expression, because all of these elements contribute to clonal deletion. As in clonal deletion models, and as predicted by the down-regulation of NF-κB, PAH-induced death of pro/pre-B cells was at least partially dependent on c-Myc down-regulation. Furthermore, whereas dexamethasone induced a G0/G1 cell cycle arrest, PAH had no effect on pro/pre-B cell growth, indicating that growth arrest and apoptosis occur by separable signaling pathways in this early phase of B cell development. Finally, in contrast to clonal deletion, PAH-induced pro/pre-B cell death was not dependent on p27Kip1 or p21WAF1 up-regulation but did coincide with p53 induction. These results distinguish the PAH-induced apoptosis pathway from that activated during clonal deletion and indicate that signaling cascades leading to growth arrest and/or apoptosis in pro/pre-B cells differ from those active at later B cell developmental stages.

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Section: Figurecontrasting

confidence: 47%

Environmental Chemical-Induced Pro/Pre-B Cell Apoptosis: Analysis of c-Myc, p27Kip1, and p21WAF1 Reveals a Death Pathway Distinct from Clonal Deletion

Ryu

Mann

Schlezinger

et al. 2003

The Journal of Immunology

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“…mIgM crosslinking in unsynchronized murine B-lymphoma cells (such as WEHI-231, CH31, and ECH408), leads to a transient increase in c-myc mRNA and protein within one to two hours, and a decrease to much below the baseline level at four to eight hours [38][39][40]. Human Burkitt's lymphoma cells also down-regulate c-Myc upon mIgM crosslinking [41]. IgD crosslinking, on the other hand, also leads to a transient increase in c-Myc, but the levels of mRNA and protein never drop below the baseline levels ( [39]; Liu et al, in preparation).…”

Section: The Role Of Ras In Bcr Signalingmentioning

confidence: 99%

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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“…In contrast, in other experimental models, apoptosis induction is related to the inhibition of c-myc expression, 39 and sometimes to growth arrest. 40 Particularly in rat hepatocarcinoma cells, c-myc blockade leads to growth inhibition and induction of differentiation 41 ; in addition, in F9 cells, induced to differentiate by RA, the c-myc decrease is closely linked to differentiation. 42 In our model, we observed a decrease in c-myc (inversely proportional to RA concentration): this reduction may depend more on the differentiating effect of RA than on the induction of apoptosis, similar to observations with hepatocarcinoma and F9 cells.…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid treatment induces apoptosis or expression of a more differentiated phenotype on different fractions of cultured fetal rat hepatocytes

et al. 1998

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The present study reports the effects of retinoic acid (RA) on cultured fetal rat hepatocytes. We show that RA treatment induces both differentiation and apoptosis. Hepatocytes cultured for 48 hours in the presence of 5 mol/L RA form junctional complexes in the areas of contact between neighboring cells and develop bile canaliculi, typical features of mature and well-differentiated cells. At the same time, about 20% of cells are induced to die by apoptosis, and the percentage of apoptotic cells increases according to the concentration of RA used and the duration of treatment. The induction of apoptosis, studied at the morphological and biochemical levels, revealed that, in our system, the classical compaction of chromatin occurs only during the final stages of the process; instead of the common marker of apoptosis, i.e., the ''DNA ladder'' pattern of fragmentation, megabase-sized fragments were found. These observations provide further evidence of the existence of fundamental differences in the mechanisms of apoptosis among cell types. To investigate the molecular mechanism of the effects of RA, we evaluated the expression of two proteins, c-myc and p53, which are known to be involved in both cell differentiation and apoptosis. The data obtained show that the amount of p53 remained unchanged after RA treatment. On the contrary, a dose-dependent reduction in c-myc levels was found, suggesting that RA action may be mediated by modulation of this oncogene. Our findings regarding the apoptosis-inducing effect of RA, which was not found in adult hepatocytes, suggest a possible relationship between this phenomenon and the proliferative capacity and/or differentiation state of hepatocytes. (HEPATOLOGY 1998;28: 727-737.) Natural and synthetic retinoids, members of the vitamin A family, are compounds with numerous pleiotropic effects.

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Anti-IgM-mediated Regulation of c-myc and Its Possible Relationship to Apoptosis

Cited by 50 publications

References 86 publications

Environmental Chemical-Induced Pro/Pre-B Cell Apoptosis: Analysis of c-Myc, p27Kip1, and p21WAF1 Reveals a Death Pathway Distinct from Clonal Deletion

Environmental Chemical-Induced Pro/Pre-B Cell Apoptosis: Analysis of c-Myc, p27Kip1, and p21WAF1 Reveals a Death Pathway Distinct from Clonal Deletion

Activation-induced cell death in B lymphocytes

Retinoic acid treatment induces apoptosis or expression of a more differentiated phenotype on different fractions of cultured fetal rat hepatocytes

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