The Transcriptional Regulation Of GM-CSF By BCL10

Granulocyte macrophage colony-stimulating factor(GM-CSF)is a multipotent cytokine involved in the production and function of the hematopoietic cell.GM-CSF plays a major role in response to infection and physiological and pathological inflammatory processes.The expression of GM-CSF gene is controlled both in transcriptional and translational level,but primary regulated at transcriptional state.B-cell lymphoma 10(BCL10)gene was found in chromosomal dislocation in the cell of mucosa-associated lymphoid tissue(MALT)lymphoma. The chromosomal dislocation makes the bcl10 gene under the control of the enhancer of Ig, leading to over expression of bcl10.previous studies have shown that BCL10 involved in the activation of NF-κB signal pathway,and induce the cell apoptosis.In this study,on the base of producing the constructs including pcDNA1-BCL10,pGL2-GMCSFpr,pGL2-GMCSFpr/en, pGL2-GMCSFpr-basic,pGL2-GMCSFpr-mNFAT,pGL2-GMCSFpr-mETS1, pGL2-GMCSFpr-mAP1,and pGL2-GMCSFpr-mETS1/mNFAT,We transfer these plasmids to the cell of K562.The results demonstrate,1)BCL10 activates the transcription of GM-CSF in K562,and improved by ionomycin.2)The binding site of ETS1 is necessary for the transcriptional activation of GM-CSF by BCL10.The normal concentration of the ETS1 and AP1 are essential to the transcriptional activation of GM-CSF by BCL10,however,the over expression of ETS1 lead to repression of the transcriptional activation of GM-CSF by BCL10.3)The transcriptional activation of GM-CSF by BCL10 is in a way independent from the NF-κB signal pathway. We investigated the promoter region of atxl,which encodes a copper chaperone in response to iron deficiency induction.Deletion analysis of the promoter region from 5' and 3' ends revealed that the -532/-461 and -320 /-276 regions were necessary and sufficient for iron deficiency-inducible expression.Further deletion analysis showed that two of the Fe deficiency responsive elements(FeREs)localized within the -532/-511 and -306/-276 regions, in which AtxFeRE1 at -529/-515(GTCGCACTGGCATGT)and AtxFeRE2 at -300/-286 (GCAGCGATGGCATTT)had been identified respectively,with a conserved sequence of GNNGCNNTGGCATNT,differing from all known FeREs found in other organisms.