CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

Rutberg, Susan; Adams, Tracey L.; Olive, Michelle; Alexander, Nathan; Vinson, Charles; Yuspa, Stuart H.

doi:10.1038/sj.onc.1202463

Cited by 47 publications

(52 citation statements)

References 47 publications

(57 reference statements)

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“…Members of the CREB family of proteins have also been shown to bind activator protein (AP-1) target DNA sequences, thus inhibiting AP-1-mediated transcription in differentiating keratinocytes (18,37). We (49,51) and others (56) have found evidence to support a role for diminished CREB repressor activity in hypoxia-induced expression of proinflammatory genes such as TNF-␣ in intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner

O’Reilly

Leonard²,

Kieran³

et al. 2006

American Journal of Physiology-Cell Physiology

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Hypoxia occurs during a number of conditions in which altered epithelial proliferation is critical, including tumor development. Microarray analysis of colon-derived epithelial cells revealed a hypoxia-dependent increase in the expression of amphiregulin, an EGF receptor (EGFR) ligand that activates epithelial proliferation and has been associated with the development of colonic tumors. Amphiregulin expression was also induced in tissues from mice exposed to whole animal hypoxia. The hypoxic upregulation of amphiregulin was independent of the classic transcriptional response mediated via hypoxia-inducible factor (HIF)-1α. Transfection of HeLa cells with truncated amphiregulin promoter reporter constructs revealed that a 37-bp segment upstream from the TATA box retained hypoxic sensitivity. This sequence contains an evolutionarily conserved cAMP response element (CRE) that constitutively binds the CRE binding protein (CREB). Deletion of the CRE abolished sensitivity to hypoxia. Thus hypoxia promotes intestinal epithelial amphiregulin expression in a CRE-dependent manner, an event that may contribute to increased proliferation. These data also further support a role for CREB as an HIF-independent hypoxia-responsive transcription factor in the regulation of intestinal epithelial gene expression.

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Section: Discussionmentioning

confidence: 99%

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner

O’Reilly

Leonard²,

Kieran³

et al. 2006

American Journal of Physiology-Cell Physiology

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“…This suggests that CREB activity is progressively recruited during neuronal differentiation in the embryonic spinal cord. Although CREB is mostly known as an activator, it has been found to inhibit transcription, and whether it acts as a repressor depends on its phosphorylation status (41), the partners recruited in transcriptional complexes (42), and the regulatory region of the gene to which CREB binds (43). Alternatively, CREB negative effect on gli1 transcription may be indirect by inducing expression of a repressor (44).…”

Section: Discussionmentioning

confidence: 99%

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

Belgacem

Borodinsky

2015

Proc. Natl. Acad. Sci. U.S.A.

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Sonic hedgehog (Shh) is a morphogenic protein that operates through the Gli transcription factor-dependent canonical pathway to orchestrate normal development of many tissues. Because aberrant levels of Gli activity lead to a wide spectrum of diseases ranging from neurodevelopmental defects to cancer, understanding the regulatory mechanisms of Shh canonical pathway is paramount. During early stages of spinal cord development, Shh specifies neural progenitors through the canonical signaling. Despite persistence of Shh as spinal cord development progresses, Gli activity is switched off by unknown mechanisms. In this study we find that Shh inverts its action on Gli during development. Strikingly, Shh decreases Gli signaling in the embryonic spinal cord by an electrical activity- and cAMP-dependent protein kinase-mediated pathway. The inhibition of Gli activity by Shh operates at multiple levels. Shh promotes cytosolic over nuclear localization of Gli2, induces Gli2 and Gli3 processing into repressor forms, and activates cAMP-responsive element binding protein that in turn represses gli1 transcription. The regulatory mechanisms identified in this study likely operate with different spatiotemporal resolution and ensure effective down-regulation of the canonical Shh signaling as spinal cord development progresses. The developmentally regulated intercalation of electrical activity in the Shh pathway may represent a paradigm for switching from canonical to noncanonical roles of developmental cues during neuronal differentiation and maturation.

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“…Binding of CREB to ARE usually represses gene expression by interfering with the transcriptional activities of AP-1 (63,64). In our studies, CREB strongly and specifically bound to the CRE sequence but not to the ARE (Fig.…”

Section: Discussionmentioning

confidence: 99%

cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor

Chakraborty

Maity

Sil

et al. 2009

Journal of Biological Chemistry

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Little is known about the regulation of the innate host defense peptide cathelicidin at the mucosal surfaces. Expression is believed to be transcriptionally regulated, and several cis-acting elements have been identified in the cathelicidin putative promoter. However, the trans-acting factors have not been clearly defined. We have recently reported that bacterial exotoxins suppress cathelicidin expression in sodium butyrate-differentiated intestinal epithelial cells (ECs), and this may be mediated through inducible cAMP early repressor. Here we have shown that cAMP-signaling pathways transcriptionally regulate cathelicidin expression in various ECs. cAMP-response elementbinding protein (CREB) and AP-1 (activator protein-1) bind to the cathelicidin putative promoter in vitro. Additionally, transcriptional complexes containing CREB, AP-1, and cathelicidin upstream regulatory sequences are formed within ECs. We have also shown that these complexes may activate cathelicidin promoter and are required for its inducible expression in ECs. This is underscored by the fact that silencing of CREB and AP-1 results in failure of ECs to up-regulate cathelicidin, and hepatitis B virus X protein may use CREB to induce cathelicidin. On the other hand, inducible cAMP early repressor competes with CREB and AP-1 for binding to the cathelicidin promoter and represses transcription, thus functioning as a counter-regulatory mechanism. Finally, both CREB and AP-1 were shown to play major roles in the regulation of cathelicidin in sodium butyrate-differentiated HT-29 cells. This is the first report of a detailed mechanistic study of inducible cathelicidin expression in the mucosal ECs. At the same time, it describes a novel immunomodulatory function of cAMP.

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CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

Cited by 47 publications

References 47 publications

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner

Inversion of Sonic hedgehog action on its canonical pathway by electrical activity

cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor

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