Gene regulation of the @entity563 proteinase inhibitors alpha1-antitrypsin and XXXX .

@entity1 @entity32 @entity6417 @entity650 @entity1003 @entity9255 @entity8698 @entity563
The @entity563 proteinase inhibitors (serpins) are a superfamily of proteins with a diverse set of functions, including the control of @entity1003 , complement activation, programmed cell death and development. The most abundant serpins in @entity1 plasma are @entity6417 ( @entity6417 ) and @entity8698 (ACT). During @entity32 , circulating levels can increase by up to 3-fold for the former and by 4-5-fold for the latter. The major site for increased synthesis is the liver. Other tissues, such as the lung, are also capable of synthesizing @entity6417 and ACT, and expression can be increased by up to 100-fold by cytokines. There is a tissue-specific promoter for the liver, and alternative promoters for other tissues that express @entity6417 . Basal @entity6417 expression is regulated by the synergistic action of the tissue-specific transcription factors hepatocyte nuclear factors 1alpha and 4. An enhancer positioned approx. 1.2 kb from the end of the last exon in the 3' flanking sequence modulates cytokine-induced expression by @entity650 and @entity9255 . Microcell hybrid transfection studies have shown that a sequence containing 15 kb of 5' flanking sequence is sufficient to allow stable expression of @entity6417 in a position-independent manner. There is probably a single promoter for ACT. @entity9255 -inducible elements have been identified in the 5' flanking sequence approx. 100 bp upstream from the transcription initiation site, and a further interleukin-1-responsive enhancer has been identified approx. 13 kb upstream. The pathways for a humoral response are being mapped at high resolution.
