An Extended α-Helix and Specific Amino Acid Residues Opposite the DNA-binding Surface of the cAMP Response Element Binding Protein Basic Domain Are Important for Human T Cell Lymphotropic Retrovirus Type I Tax Binding

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.

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

Circulation ◽

10.1161/01.cir.92.8.2041 ◽

1995 ◽

Vol 92 (8) ◽

pp. 2041-2043 ◽

Cited By ~ 35

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

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Antisense‐induced knockdown of cAMP response element‐binding protein downregulates Per1 gene expression in the shell region of nucleus accumbens resulting in reduced alcohol consumption in mice

Alcoholism Clinical and Experimental Research ◽

10.1111/acer.14687 ◽

2021 ◽

Author(s):

Rishi Sharma ◽

Vaibhav Mishra ◽

Meet Parikh ◽

Anshul Soni ◽

Pradeep Sahota ◽

...

Keyword(s):

Gene Expression ◽

Nucleus Accumbens ◽

Alcohol Consumption ◽

Binding Protein ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Response Element ◽

Element Binding Protein ◽

Shell Region

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Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽

10.3390/toxins13050329 ◽

2021 ◽

Vol 13 (5) ◽

pp. 329

Author(s):

Andrew Holmes ◽

Jessie Sadlon ◽

Keith Weaver

Keyword(s):

Amino Acid ◽

Enterococcus Faecalis ◽

Host Response ◽

Cytoplasmic Membrane ◽

Transmembrane Domain ◽

The Other ◽

Type I ◽

Transcriptomic Response ◽

Specific Amino Acid ◽

Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

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