Interactions between CBP, NF-κB, and CREB in the lungs after hemorrhage and endotoxemia

Shenkar, Robert; Yum, Ho-Kee; Arcaroli, John J.; Kupfner, John; Abraham, Edward

doi:10.1152/ajplung.2001.281.2.l418

Cited by 61 publications

(50 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunohistochemistry of phosphorylated Erk1/Erk2 (e) and phosphorylated CREB (f, g) in lung tumor T2 (e, f) and T4 (g). Immunohistochemistry was performed as described in Figure 1 using a 1 : 100 dilution of the primary antibodies activated in lungs in response to insults such as hemorrhage (Shenkar and Abraham, 1999;Abraham et al, 2001;Shenkar et al, 2001), endotoxemia (Shenkar and Abraham, 1999;Abraham et al, 2001;Shenkar et al, 2001), hyperoxia (George et al, 1999) and metal exposure (Samet et al, 1998) and is important for normal lung development (Rudolph et al, 1998), its role in lung tumorigenesis has not been reported.…”

mentioning

confidence: 99%

Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma

et al. 2003

View full text Add to dashboard Cite

Elevated levels of insulin-like growth factor (IGF)-II are associated with a poor prognosis in human pulmonary adenocarcinoma; however, a causal role for IGF-II in pulmonary adenocarcinoma has not been demonstrated. Here, we show that transgenic overexpression of IGF-II in lung epithelium induces lung tumors in 69% of mice older than 18 months of age. These tumors displayed morphological characteristics of human pulmonary adenocarcinoma such as their epithelial origin, tubulo-acinar architecture and expression of TTF-1, SP-B and proSP-C. Examination of signaling molecules downstream of the IGF-IR showed the activation of either the Erk1/Erk2 or p38 MAPK pathways, but not both, within the lung tumors. Notably, all lung tumors contained high levels of phosphorylated CREB, suggesting that both the Erk1/ Erk2 and p38 MAPK pathways converged on this transcription factor. Moreover, IGF-II induced proliferation and CREB phosphorylation in human lung cancer cell lines, suggesting that IGF-II and CREB also contribute to the growth of human lung tumors. Thus, IGF-II is an important genetic factor in the development of lung tumorigenesis, in which activation of CREB is a ubiquitous event. The MMTV-IGF-II transgenic mice provide a critical model for elucidating the role of IGF-II in this fatal human disease.

show abstract

mentioning

confidence: 99%

Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma

et al. 2003

View full text Add to dashboard Cite

show abstract

“…It has been suggested that the bromodomain recognizes acetylated residues and could function in identification of different acetylated domains. The CH domains and the (142,147).…”

Section: Role Of Cbp In Cxcl1 Transcriptionmentioning

confidence: 99%

“…The CH domains and the KIX domain are thought to mediate protein-protein interaction (146). The KIX domain is involved in the interaction between CBP and the p65 (Rel A) subunit of NF-κB, as well as CBP binding to the transcriptionally active serine-133-phosphorylated form of CREB (142,147).…”

Section: Role Of Cbp In Cxcl1 Transcriptionmentioning

confidence: 99%

“…It has been suggested that the bromodomain recognizes acetylated residues and could function in identification of different acetylated domains. The CH domains and the (142,147).CBP also appears to be under cell cycle control. Many kinases such as PKA, calcium/ calmodulin-dependent kinase, MAP kinase, and cyclin-dependent kinases Cdk2 and Cdc2 have been implicated in the positive and negative phosphorylation control of CBP.…”

mentioning

confidence: 99%

“…Yet another model proposes that CBP may take advantage of either its intrinsic HAT activity or other HATs assembled in multi-component complexes to target the chromatin and/or transcription factors for transcription activation. Even though targets of CBP in vivo are yet to be identified, in vitro studies have shown that CBP can acetylate all four core histones (149).More recently, acetylation of transcription factors such as p53, E2F-1, 2, and 3, MYB, MyoD, GATA-1, CREB, and NF-κB (142,147,150,151) by CBP has been reported and, in almost all cases, the acetylation led to enhanced DNA-binding activity. It is possible that acetylation regulates protein-protein interaction or facilitates protein-DNA binding by changing the conformation of the protein and introducing a DNA-recognition surface (146).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Fine Tuning the Transcriptional Regulation of the CXCL1 Chemokine

Amiri¹,

Richmond²

2003

Progress in Nucleic Acid Research and Molecular Biology Volume 74

View full text Add to dashboard Cite

Constitutive activation of the transcription factor nuclear factor-κB (NF-κB) plays a major role in inflammatory diseases as well as cancer by inducing the endogenous expression of many proinflammatory proteins such as chemokines, and facilitating escape from apoptosis. The constitutive expression of chemokines such as CXCL1 has been correlated with growth, angiogenesis, and metastasis of cancers such as melanoma. The transcription of CXCL1 is regulated through interactions of NF-κB with other transcriptional regulatory molecules such as poly(ADP-ribose) polymerase-1 (PARP-1) and cAMP response element binding protein (CREB)-binding protein (CBP). It has been proposed that these two proteins interact with NF-κB and other enhancers to form an enhanceosome at the promoter region of CXCL1 and modulate CXCL1 transcription. In addition to these positive cofactors, a negative regulator, CAAT displacement protein (CDP), may also be involved in the transcriptional regulation of CXCL1. It has been postulated that the elevated expression of CXCL1 in melanomas is due to altered interaction between these molecules. CDP interaction with the promoter down-regulates transcription, whereas PARP and/or CBP interactions enhance transcription. Thus, elucidation of the interplay between components of the enhanceosome of this gene is important in finding more efficient and new therapies for conditions such as cancer as well as acute and chronic inflammatory diseases. I. Chemotactic CytokinesChemokines are small, proinflammatory, inducible, secreted cytokines that are involved in trafficking, activation, and proliferation of many cell types such as myeloid, lymphoid, pigment epidermal, and endothelial cells (1). Chemokine proteins are encoded by 70-130 amino acids, which also include a signal peptide sequence of 20-25 amino acids. It is interesting to note that although chemokines share little homology in their primary sequence, their overall tertiary structure is similar (2). Chemokines have been observed to form dimers in concentrated solutions and on crystallization, however, these concentrations are much higher than the biological concentrations. It is now commonly accepted that chemokines act as monomers in biological systems (2-4). To date, over 50 chemokines have been identified and assigned to four classes according to their arrangement of the first two of four conserved cysteine residues: C, CC, CXC, and CX 3 C chemokines (Table I). The C chemokines such as lymphotactin (XCL1) lack two of the four conserved cysteine residues, whereas CC chemokines have the first two cysteines adjacent to each other; examples are chemoattractant protein-1 (CCL2), macrophage inflammatory protein-1α (CCL3), and Copyright 2003, Elsevier (USA). All rights reserved. NIH Public Access Author ManuscriptProg Nucleic Acid Res Mol Biol. Author manuscript; available in PMC 2011 July 20. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript regulated upon activation of normal T cells expressed and secreted (CCL5). In CX 3 C ch...

show abstract

Transcriptional regulation of IL‐8 by iron chelator in human epithelial cells is independent from NF‐κB but involves ERK1/2‐ and p38 kinase‐dependent activation of AP‐1

Choi¹,

Park²,

Choi³

et al. 2007

J of Cellular Biochemistry

View full text Add to dashboard Cite

We have shown that the bacterial iron chelator, deferoxamine (DFO), triggers inflammatory signals including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs) by activating the ERK1/2 and p38 kinase pathways. In this study we investigated the mechanisms involved in IL-8 generation by DFO, focusing on the transcription factors involved and the roles of both mitogen-activated protein kinases (MAPKs) in the transcription factor activation. Treatment of human epithelial HT-29 cells with DFO markedly up-regulated the expression of the essential components of the transcription factor AP-1 at a transcriptional level, while it minimally affected the expression of the NF-kappaB subunits. DFO also induced AP-1-dependent transcriptional activity in HT-29 cells, and this activity was further augmented by the wild-type c-Jun transfection. In contrast, the AP-1 activity by DFO was markedly decreased by the dominant-negative c-Jun transfection. Electrophoretic mobility shift assays revealed that DFO increases the specific binding of AP-1 but not of NF-kappaB. Such AP-1 binding and transcriptional activities were blocked by the inhibitors of the ERK1/2 and p38 kinase pathways, suggesting that both mitogen-activated protein kinases (MAPKs) lie upstream of AP-1. Besides its action on AP-1, DFO also induced the specific binding of other transcription factors such as CREB and Egr-1. In summary, our results indicate that iron chelator-induced IL-8 generation in IECs involves activation of ERK1/2 and p38 kinase and downstream activation of AP-1. A possible link between iron status and two additional transcription factors, that is, CREB and Egr-1, rather than NF-kappaB, was also suggested.

show abstract

Interactions between CBP, NF-κB, and CREB in the lungs after hemorrhage and endotoxemia

Cited by 61 publications

References 38 publications

Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma

Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma

Fine Tuning the Transcriptional Regulation of the CXCL1 Chemokine

Transcriptional regulation of IL‐8 by iron chelator in human epithelial cells is independent from NF‐κB but involves ERK1/2‐ and p38 kinase‐dependent activation of AP‐1

Contact Info

Product

Resources

About