Modulation by cellular cholesterol of gene transcription via the cyclic AMP response element11Abbreviations: cAMP, adenosine 3′,5′-cyclic monophosphate; CHO, Chinese hamster ovary; CRE, cyclic AMP response element; FBS, foetal bovine serum; MβCD, methyl-beta-cyclodextrin: PKA, protein kinase A; SPAP, secreted placental alkaline phosphatase.

2001 ◽  
Vol 62 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Aliya Middleton ◽  
David Nury ◽  
Susan J Willington ◽  
Liaque Latif ◽  
Stephen J Hill ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Chinese Hamster ◽  
Placental Alkaline Phosphatase ◽  
Cellular Cholesterol ◽  
Beta Cyclodextrin ◽  
Cyclic Amp Response Element ◽  
Foetal Bovine Serum ◽  
Kinase A

scholarly journals Doxorubicin-induced Id2A gene transcription is targeted at an activating transcription factor/cyclic AMP response element motif through novel mechanisms involving protein kinases distinct from protein kinase C and protein kinase A.

1995 ◽  
Vol 15 (11) ◽  
pp. 6386-6397 ◽  
Author(s):  
M Kurabayashi ◽  
S Dutta ◽  
R Jeyaseelan ◽  
L Kedes
Keyword(s):  
Transcription Factor ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Dependent Protein Kinase ◽  
Kinase C ◽  
Dependent Protein ◽  
Cyclic Amp Response Element ◽  
Uv Response ◽  
Activating Transcription Factor ◽  
Kinase A

We have recently shown that doxorubicin (Dox), an antineoplastic drug and an inhibitor of terminal differentiation of myogenic and adipogenic cells, induces expression of Id, a gene encoding a helix-loop-helix transcriptional inhibitor. In this study we have investigated the molecular mechanisms underlying Dox-induced Id2A expression. We have also attempted to determine whether the genetic responses to Dox are related to the UV response, a well-characterized set of reactions to UV and DNA-damaging compounds that is partly mediated by AP-1. Transient transfection of a series of deletions and point mutation derivatives of the human Id2A promoter sequence shows that two closely spaced and inverted short elements similar to an activating transcription factor (ATF) binding site or a cyclic AMP response element (CRE) are necessary and sufficient for a full response to Dox. We refer to this element as the IdATF site. Sequences containing an IdATF site conferred Dox inducibility on a minimal heterologous promoter. An electrophoretic mobility shift assay showed nuclear proteins specifically interacting with the IdATF sequence. While oligonucleotides containing either legitimate ATF/CRE or AP-1 binding sequences competed for binding, antibody supershift experiments suggested that neither CREB/ATF-1 nor AP-1 are major factors binding to IdATF. Several independent criteria suggest that Dox inducibility was independent of Ca2+/phospholipid-dependent protein kinase (protein kinase C), cyclic AMP-dependent protein kinase (protein kinase A), and tyrosine kinase. Moreover, we found that Dox also induces transcription from promoters of immediate-early genes through an AP-1-independent pathway. Taken together, our results suggest that Dox elicits a novel genetic response distinct from the classical UV response.

Sign in / Sign up

Export Citation Format

Share Document