Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts.

Abstract

A DNA-binding factor with properties of NF-KB and another similar activity are rapidly induced when growth-arrested BALB/c 3T3 ceUs are stimulated with serum growth factors. Induction of these DNA-binding activities is not inhibited by pretreatment of quiescent ceUs with the protein synthesis inhibitor cycloheximide. Interestingly, the major NF-KB-like activity is not detected in nuclear extracts of proliferating ceUs, and thus its expression appears to be limited to the Go-to-G1 transition in 3T3 ceUs. These DNA-binding activities bind many of the expected NF-cB target sequences, including elements in the class I major histocompatibility complex and human immunodeficiency virus enhancers, as weUl as a recently identified NF-cB binding site upstream of the c-myc gene. Furthermore, both the class I major histocompatibility complex and c-myc NF-KcB binding sites confer inducibility on a minimal promoter in 3T3 cells stimulated with serum growth factors. The results demonstrate that NF-KB-like activities are immediate-early response proteins in 3T3 cells and suggest a role for these factors in the Go-to-G1 transition.Much of our knowledge concerning the signals that are activated following the interaction of serum growth factors with their receptors and that are involved in the stimulation of cell growth has been generated by using serum-deprived BALB/c 3T3 fibroblasts. In the absence of serum growth factors, 3T3 cells enter a state called Go in which growth and cell division stop. The addition of growth factors initiates a complex series of events which causes cells to enter G1 and which culminates in the synthesis of DNA and cell division (1,13,15,16,18,29,41). During the GO-to-G1 transition, the expression of several transcription factors, including those encoded by certain proto-oncogenes, is activated, and these gene products play a critical role in initiating and controlling cell growth and DNA synthesis (13, 15-18, 28, 32, 38, 41, 48, 50, 58, 64). Aberrant expression of these proto-oncogenes, such as c-fos or c-myc, is implicated in the pathogenesis of a variety of neoplasms (21,39).NF-KB is a DNA-binding protein originally identified as a B-cell-specific factor involved in the control of expression of immunoglobulin kappa genes (59). Subsequently, regulatory elements in or upstream of various genes involved in immune function or in inflammation and elements in certain viruses such as the human immunodeficiency virus (HIV) have been shown to interact with NF-KB and to be critical for appropriate regulated or cell-type-specific gene expression (7,11,20,23,30,34,42,43,45,49,53,55,67). NF-KB DNA-binding activity can be induced in certain cell types with the cytokines tumor necrosis factor alpha and interleukin-1 (34, 42, 46, 52, 61), with the phorbol ester phorbol myristate acetate (PMA) (60), by virus infection, and by double-stranded RNA treatment (23,42,43,67). Furthermore, NF-KB DNA-binding activity is activated by treatment of pre-B cells and Jurkat T cells with mitogens (11,20,49,60 inhibitor IKB (2,3,...

NF-κB decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis

“…Some have reported that NF-κB activation is necessary to cause cell cycle arrest (Bash et al, 1997). However the body of evidence in recent studies have shown that NF-κB activation is related to cell cycle progression rather than arrest in various cell types (Baldwin et al, 1991;Cressman et al, 1994;Yamada et al, 1997), and that NF-κB inhibition results in cell cycle arrest (Kaltschmidt et al, 1999;Otsuka et al, 1999). Radiation has bi-directional effects on p53; it can activate p53 via ATM (Herzog et al, 1998;Jonathan et al, 1999) and simultaneously activates NF-κB (Li and Karin, 1998), which may have an inhibitory effect on p53 (Stoffel et al, 2004).…”

Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins.

“…NF-KB has a primary role in immune function and inflammation, in lymphoid differentiation, and in embryonic axis determination in insects (Grimm and Baeuerle 1993;Liou and Baltimore 1993;Siebenlist et al 1994;Thanos and Maniatis 1995;Verma et al 1995). There is also evidence that NF-KB plays a role in mitogenic signal transduction (Miyamoto et al 1994) and programmed cell death (Baldwin et al 1991;Beauparlant et al 1994). Furthermore, knockouts of ei ther p50, c-rel, or RelB indicate that NF-KB is critical for specific and nonspecific immune response and cell divi sion (Kontgen et al 1995;Sha et al 1995;Weih et Luciferase activity was determined 24 hr after transfection and the c-Jun transcriptional activity assayed as described in Materials and Methods.…”

Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells

“…After 24 h, the medium was changed to SFM and the cells were then cotransfected with a plasmid containing the NF-kB-luciferase reporter (a gift from Dr T Gilmore, Boston University, MA, USA) (Baldwin Jr et al, 1991) and pRL-TK-Luc vector, an internal control for transfection efficiency, using Fugene 6 (Roche, Berkeley, CA, USA) according to the manufacturer's procedure. At 48 h after transfection, the cells were lysed for luciferase assay using the Dual-luciferase reporter assay system (Promega, WI, USA).…”