Wg. Butscher et al., Targeting of p300 to the interleukin-2 promoter via CREB-Rel cross-talk during mitogen and oncogenic molecular signaling in activated T-cells, J BIOL CHEM, 276(29), 2001, pp. 27647-27656
In this report, we explore the mechanisms of targeting of p300 to the inter
leukin-2 (IL-2) promoter in response to mitogenic and oncogenic molecular s
ignals. Recruitment of p300 by cAMP-responsive element-binding protein-Rel
cross-talk at the composite CD28 response element (CD28RE)-TRE element of t
he IL-2 promoter is essential for promoter inducibility during T-cell activ
ation, and CD28RE-TRE is the exclusive target of the human T-cell lymphotro
pic virus type I oncoprotein Tax. The intrinsic histone acetyltransferase a
ctivity of p300 is dispensable for activation of the IL-2 promoter, and the
N-terminal 743 residues contain the minimal structural requirements for sy
nergistic transactivation of the CD28RE-TRE, the IL-2 promoter, and endogen
ous IL-2 gene expression. Mutational analysis of p300 reveals differential
structural requirements for the N-terminal p300 module by individual cis-el
ements within the IL-2 promoter. These findings provide evidence that p300
assembles at the IL-2 promoter to form an enhanceosome-like signal transduc
tion target that is centrally integrated at the CD28RE-TRE element of the I
L-2 promoter through specific protein module-targeted associations in activ
ated T-cells.