Function of the c-Myc oncoprotein in chromatin remodeling and transcription.

Deregulated expression of the c-myc proto-oncogene contributes to malignant progression of a variety of tumors. The c-Myc protein (or Myc) is a transcription factor that positively or negatively regulates expression of distinct sets of target genes. Transcriptional activation by Myc is mediated through dimerization with Max and binding to the DNA consensus sequence CA(C/T)GTG (the E-box).

Life and death decisions in B1 lymphoma cells.

Crosslinking of surface immunoglobulin (Ig) receptors with anti-IgM (anti-mu) but not anti-IgD (anti-delta) antibodies causes growth arrest and apoptosis in several extensively characterized B1-like lymphoma cell lines. While anti-mu stimulates a transient increase in c-myc mRNA and protein expression, followed by a rapid decline below the baseline level, anti-delta only causes a moderate increase in the expression of this oncogene, which returns to baseline levels within 24-48 hours. However, signals downstream from anti-delta can be converted into an apoptotic pathway by modulating PI3K activity, suggesting that PI3K is a critical rheostat controlling survival signals in B1 cell lines.

B-cell receptor and Fas-mediated signals for life and death.

A series of B-cell lymphoma lines with an immature phenotype has been used as a model system to study molecular events associated with receptor ligation induced death. B-cell receptor (BCR) cross-linking with antibodies to membrane IgM (but not with anti IgD) induces c-Myc downregulation via nuclear factor kappaB inactivation and p27(Kip1) accumulation in these B lymphomas. Anti-mu-treated cells then undergo G1 arrest and die by apoptosis independent of Fas.

Activation-induced cell death in B lymphocytes.

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 activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR).

Regulation of the G1 phase of the mammalian cell cycle.

In any multi-cellular organism, the balance between cell division and cell death maintains a constant cell number. Both cell division cycle and cell death are highly regulated events. Whether the cell will proceed through the cycle or not, depends upon whether the conditions required at the checkpoints during the cycle are fulfilled.

Steroid- and retinoid-mediated growth arrest and apoptosis in WEHI-231 cells: role of NF-kappaB, c-Myc and CKI p27(Kip1).

IgM cross-linking induces NF-kappaB inactivation, c-Myc down-regulation, and cyclin kinase inhibitor p27(Kip1) accumulation in WEHI-231 murine B lymphoma cells. p27(Kip1) up-regulation leads to a decreased cyclin-dependent kinase 2 activity, retinoblastoma protein hypophosphorylation, G1 arrest and apoptosis. Similar to membrane (m) IgM cross-linking in B lymphoma cells, steroids and retinoids down-regulate c-Myc (via NF-kappaB inactivation) and induce apoptosis in T cell hybridomas and thymocytes.

Regulation of p27Kip1 accumulation in murine B-lymphoma cells: role of c-Myc and calcium.

IgM cross-linking induces G1 arrest and apoptosis in murine B-lymphoma cells. It prevents pRb phosphorylation by decreasing cyclin-dependent kinase 2 activity via the up-regulation of cyclin kinase inhibitor p27Kip1. Anti-IgM also causes an increase in cytosolic free calcium and a loss of c-myc mRNA and protein.

Primary structure of ovine fibroblast growth factor-1 deduced by protein and cDNA analysis.

The amino acid sequence of full-length ovine fibroblast growth factor-1 (FGF-1) was determined by a combination of protein and cDNA sequencing. FGF-1 cDNA analysis indicated that ovine kidney cells express mRNAs encoding both full-length FGF-1 and a truncated FGF-1 variant. An overall comparison of the ovine FGF-1 primary sequence to the eight species studied to date revealed a high degree of conservation, with ovine FGF-1 sharing 90 and 95% sequence identity with human FGF-1 and bovine FGF-1, respectively.

Role of c-myc and p27 in anti-IgM induced B-lymphoma apoptosis.

Crosslinking membrane IgM receptors on a set of murine B cell lymphomas leads to a rapid increase in c-myc, followed by a decrease in its expression to undetectable levels by 8-24 hours. These cells die soon thereafter via apoptosis. IgD receptor crosslinking also leads to an increase in c-myc expression, but it remains above baseline levels for more than 24 hours; these cells continue to proliferate and do not die.