Autoregulation of I kappa B alpha activity.

Chiao, Paul J.; Miyamoto, Shigeki; Verma, Inder M.

doi:10.1073/pnas.91.1.28

Cited by 403 publications

(320 citation statements)

References 38 publications

Supporting

Mentioning

310

Contrasting

Order By: Relevance

“…Together, these results suggest that sodium butyrate may inhibit the translocation of NF-B factors from the cytoplasm to the nucleus. The increase in NF-B binding on treatment of the nuclear extracts with NaDOC in Figure 2C may be due to the autoregulatory induction of I B-␣ activity described previously [46][47][48][49]. The absence of NF-B binding in nuclear extracts in the absence of IL-1␤ stimulation and after NaDOC treatment demonstrates the absence of cytoplasmic contamination of the nuclear extracts.…”

Section: Treatment Of Caco-2 Cells With Sodium Butyrate Inhibits Tranmentioning

confidence: 83%

“…3A). The reappearance of I B-␣ due to autoregulatory induction [46][47][48]51] appears to be delayed in butyrate-treated cells perhaps secondary to the decrease in nuclear translocation of NF-B. Indeed, nuclear translocation NF-B has been shown to be critical for the re-expression of I B-␣ via gene transcription [46][47][48]51].…”

Section: Sodium Butyrate Induces the Protein Expression Of I B-␤ But mentioning

confidence: 99%

See 1 more Smart Citation

High-level expression of IkB-b in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role

Huang

Wen

et al. 1999

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The intestinal epithelium is spatially segregated into two compartments, one containing undifferentiated cells in a proliferative state and one with non-proliferative differentiated cells. Although this epithelium can produce many immunemodulating substances, emerging evidence suggests that the differentiated cell compartment is less immune responsive. Indeed, it is the differentiated cellular compartment that represents the interface between the highly antigenic luminal environment and the mucosal immune system. The NF-B/rel family of transcriptional activators play a critical role in regulating the inflammatory response by activating a wide variety of immune-modulating genes. These transcription factors are maintained in an inactive state in the cytoplasmic compartment by interaction with inhibitory proteins of the I B family. In this study we show by immunohistochemistry that I B-␤ is expressed at high levels specifically in the differentiated surface epithelium of the colonic mucosa. Using a naturally occurring compound found in the colon of vertebrates, butyrate, we provide evidence in an intestinal cell line that alteration of I B-␤ expression can modulate the transcriptional activation of the interleukin-8 (IL-8) gene by preventing the nuclear translocation of NF-B proteins. Therefore, the expression of I B-␤ in the differentiated surface epithelium of the colon may help these cells act as an immunological barrier to prevent activation of the mucosal immune system.

show abstract

Section: Treatment Of Caco-2 Cells With Sodium Butyrate Inhibits Tranmentioning

confidence: 83%

Section: Sodium Butyrate Induces the Protein Expression Of I B-␤ But mentioning

confidence: 99%

High-level expression of IkB-b in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role

Huang

Wen

et al. 1999

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Compared with untreated Hep3B controls (Fig. 1C, lane 1), the level of I B␣, a previously identified RelA regulated gene, 5 in the cytoplasmic extracts was stabilized by treatment with PS341 (Fig. 1C, lanes 2-6).…”

Section: Phosphorylation Of I B␣ In the Human Hcc Cell Line Hep3bmentioning

confidence: 88%

“…3,4 Previously, we cloned the murine I B␣ cDNA and promoter and described a feedback inhibition pathway for control of I B␣ gene transcription and resulting downregulation of transient activation of Rel/NF-B activity. 5 Various stim-uli can induce rapid phosphorylation of I B␣ at serine residues 32 and 36, leading to ubiquitination and degradation of I B␣. [1][2][3] Consequently, Rel/NF-B proteins are released and translocated into the nucleus where they activate the expression of target genes.…”

mentioning

confidence: 99%

Role of Rel/NF‐κB transcription factors in apoptosis of human hepatocellular carcinoma cells

Chiao¹,

Ren²,

Niu³

et al. 2002

Cancer

View full text Add to dashboard Cite

BACKGROUNDPrimary hepatocellular carcinoma (HCC) is one of the 10 most common human carcinomas in the world. The mechanism by which HCC cells resist apoptosis induced by various treatment modalities is poorly understood.METHODSThe authors sought to determine whether Rel/NF‐κB transcription factors play a key role in controlling apoptosis in human HCCcells. We assessed constitutive and inducible activation of NF‐κB in hepatitis B virus (HBV)‐positive (Hep3B) and in hepatitis virus‐negative (Chang, HepG2) HCC cells, as well as the role of known inhibitors of NF‐κB activity.RESULTSThe current study data demonstrate that 1) RelA/NF‐κB activity is activated constitutively in Hep3B cells, as determined by electrophoretic mobility shift assays; 2) RelA/NF‐κB reporter gene activity is inhibited specifically by dominant‐negative mutants of IκBα, IKK1, IKK2, MEKK1, and MEKK3 and it is activated by overexpression of wild‐type MEKK3, suggesting that upstream kinase cascades induce phosphorylation of IκBα and activate RelA/NF‐κB in Hep3B cells; 3) overexpression of the HBV x gene fails to activate NF‐κB in HepG2 and Chang cell lines; 4) The NF‐κB–inducible gene, bcl‐xl, is overexpressed in Hep3B cells and is inhibited by the proteosome inhibitor PS341, which prevents IκBα degradation and RelA/NF‐κB activation; and 5) inhibition of constitutive RelA/NF‐κB activity by PS341 sensitizes Hep3B cells to doxorubicin‐induced apoptosis.CONCLUSIONSThese results are consistent with the role of RelA/NF‐κB activity in the regulation of apoptosis through activation of its downstream target genes and suggest that signaling pathways that control RelA/NF‐κB activity may be important targets for novel therapeutic approaches in the treatment of human HCC. Cancer 2002;95:1696–705. © 2002 American Cancer Society.DOI 10.1002/cncr.10829

show abstract

“…NF-B activation can be measured by detecting protein levels of I B␣, which binds NF-B subunits in the cytoplasm and is targeted for proteosomal degradation in response to agonistic stimuli before resynthesis as an NF-B-dependent gene product (37). To determine whether GITR induces NF-B activation, I B␣ levels were analyzed from lysates of activated T cells treated with agonistic GITR-specific Ab.…”

Section: Nf-b Activation Is Triggered By Gitrmentioning

confidence: 99%

Glucocorticoid-Induced TNF Receptor, a Costimulatory Receptor on Naive and Activated T Cells, Uses TNF Receptor-Associated Factor 2 in a Novel Fashion as an Inhibitor of NF-κB Activation

Esparza

Arch

2005

The Journal of Immunology

View full text Add to dashboard Cite

Glucocorticoid-induced TNFR (GITR) has been implicated as an essential regulator of immune responses to self tissues and pathogens. We have recently shown that GITR-induced cellular events promote survival of naive T cells, but are insufficient to protect against activation-induced cell death. However, the molecular mechanisms of GITR-induced signal transduction that influence physiologic and pathologic immune responses are not well understood. TNFR-associated factors (TRAFs) are pivotal adapter proteins involved in signal transduction pathways of TNFR-related proteins. Yeast two-hybrid assays and studies in HEK293 cells and primary lymphocytes indicated interactions between TRAF2 and GITR mediated by acidic residues in the cytoplasmic domain of the receptor. GITR-induced activation of NF-κB is blocked by A20, an NF-κB-inducible protein that interacts with TRAFs and functions in a negative feedback mechanism downstream of other TNFRs. Interestingly, in contrast with its effects on signaling triggered by other TNFRs, our functional studies revealed that TRAF2 plays a novel inhibitory role in GITR-triggered NF-κB activation.

show abstract

Autoregulation of I kappa B alpha activity.

Cited by 403 publications

References 38 publications

High-level expression of IkB-b in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role

High-level expression of IkB-b in the surface epithelium of the colon: in vitro evidence for an immunomodulatory role

Role of Rel/NF‐κB transcription factors in apoptosis of human hepatocellular carcinoma cells

Glucocorticoid-Induced TNF Receptor, a Costimulatory Receptor on Naive and Activated T Cells, Uses TNF Receptor-Associated Factor 2 in a Novel Fashion as an Inhibitor of NF-κB Activation

Contact Info

Product

Resources

About