Abstract
The D-site binding protein (DBP) is a member of the proline- and acid-rich (PAR) domain subfamily of basic/leucine zipper proteins and is involved in transcriptional regulation in the liver. Deletion analysis of the DBP protein was carried out in an effort to define the function of the conserved PAR domain. Internal deletions of the protein, i.e. removing portions of the PAR domain, resulted in a substantial loss in transactivation of a high affinity DBP reporter construct when assayed in Hep G2 cells. These same sequences conferred significant transactivation to GAL4 DNA binding domain fusion proteins, indicating that this region acts as part of an independent activation domain comprised of sequences in both the amino terminus and in the PAR domain of DBP. The coexpression of full-length expression constructs for both DBP and hepatic leukemia factor resulted in a dramatic increase in activation mediated by the GAL4-DBP fusion proteins, suggesting the involvement of a regulated coactivator in this process. DBP transactivation appears to be a p300-dependent process, as a 12 S E1A expression construct disrupted DBP-mediated transactivation, and a p300 expression vector, but not a CREB binding protein vector, was able to restore DBP transactivation. These results suggest that the PAR domain is required for DBP activation, which occurs through a regulated, p300-dependent process.
Highlights
The D-site binding protein (DBP)1 is a member of the basic/ leucine zipper family (b/ZIP) and was first isolated by its ability to bind and transactivate through an element in the serum albumin promoter [1]
Through the use of deletion mutants within the context of the whole DBP protein, we have demonstrated that sequences within the central 28 amino acids of the proline- and acid-rich (PAR) domain are essential for DBP to transactivate a site from the C7␣H promoter
These results indicate that the PAR domain is critical for DBP transactivation and that a core region of close to 30 amino acids within this region is of particular importance
Summary
The D-site binding protein (DBP) is a member of the basic/ leucine zipper family (b/ZIP) and was first isolated by its ability to bind and transactivate through an element in the serum albumin promoter [1]. DBP mRNA is detected in most tissues, the protein accumulates to high levels only in the nuclei of adult liver, suggesting that it is posttranscriptionally regulated This 43-kDa protein is known to undergo a robust circadian rhythm, with its expression highest at approximately 8 p.m. In addition to the b/ZIP domain, DBP contains a distinct region termed the proline- and acid-rich (PAR) domain, which consists of a large number (16%) of proline, glutamate, and aspartate residues This unique region, found immediately amino-terminal to the basic domain, shares 83% identity with two other b/ZIP transcriptional regulators, thyrothropic embryonic factor (TEF) [10] and hepatic leukemia factor (HLF) [11, 12], and together they form the subfamily of PAR proteins. These results indicate that DBP transactivation is a p300-dependent process
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