scholarly journals Systematical analysis reveals a strong cancer relevance of CREB1-regulated genes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tianyu Zheng ◽  
Jinrong Huang ◽  
Xi Xiang ◽  
Siyuan Li ◽  
Jiaying Yu ◽  
...  
Keyword(s):  
Gene Network ◽  
Target Genes ◽  
Tumor Development ◽  
Integrative Approach ◽  
Camp Response Element ◽  
Response Element ◽  
Normal Tissues ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element ◽  
And Migration

AbstractThe transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis.

A novel cyclic AMP response element-binding protein-1 (CREB-1) splice product may down-regulate CREB-1 activity

1995 ◽  
Vol 14 (2) ◽  
pp. 191-198 ◽  
Author(s):  
M J C Ellis ◽  
H C Hurst ◽  
S Goodbourn
Keyword(s):  
Cyclic Amp ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Transactivation Domain ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Dependent Protein ◽  
Cyclic Amp Response Element ◽  
Splice Product

ABSTRACT In this report we identify novel spliced forms of cyclic AMP (cAMP) response element-binding protein-1 (CREB-1) mRNA. These forms contained an additional 17 nucleotide insert, which we refer to as the β exon, located between exons 4 and 7 of the Δ, and 5 and 7 of the α forms of CREB-1 transcript (nomenclature of Ruppert et al. 1992; EMBO Journal 11, 1503-1512). The inclusion of the β exon led to the generation of mRNAs in which the frame of CREB-1 sequences 3′ to the exon was shifted such that the encoded proteins terminate after the transactivation domain, but before the target serine for cAMP-dependent protein kinase. The β exon-containing CREB-1 mRNAs were more abundant in tissues that respond poorly to cAMP, suggesting that the generation of βCREB-1 mRNAs may contribute to the down-regulation of CREB-1 activity and cAMP responsiveness.

Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang
Keyword(s):  
Protein Kinase ◽  
Bone Pain ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Dependent Protein Kinase ◽  
Response Element ◽  
Protein Kinase Ii ◽  
Element Binding Protein ◽  
Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

cAMP Response Element Binding Protein Is Expressed and Phosphorylated in the Human Heart

Circulation ◽  
1995 ◽  
Vol 92 (8) ◽  
pp. 2041-2043 ◽  
Author(s):  
Frank Ulrich Müller ◽  
Peter Bokník ◽  
Andreas Horst ◽  
Jörg Knapp ◽  
Bettina Linck ◽  
...  
Keyword(s):  
Human Heart ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein
Sign in / Sign up

Export Citation Format

Share Document