Analysis ofElA-Mediated GrowthRegulation Functions: Binding of the300-Kilodalton Cellular Product Correlates withElA Enhancer Repression Function andDNA Synthesis-Inducing

Adenovirus ElAtransforming function requires twodistinct regions oftheprotein. Transforming activity is closely linked withthepresenceofa regiondesignated conserved domain2andtheability ofthisregion tobind theproduct ofthecelular retinoblastoma tumorsuppressor gene. We haveinvestigated thebiological properties ofthesecond transforming region ofElA,whichislocated near theN terminus. Transformationdefective mutantscontaining deletions intheN terminus (deletion ofresidues between aminoacids2and36) were deficient intheability toinduce DNA synthesis andrepressinsulin enhancer-stimulated activity. The function oftheN-terminal region correlated closely withbinding ofthe300-kilodalton ElA-associated protein andnotwithbinding oftheretinoblastoma protein. Theseresults indicate thattransformation byElA is mediated bytwofunctionally independent regions oftheprotein whichinteract withdifferent specific cellular proteins andsuggest thatthe300-kilodalton ElA-associated protein plays a majorroleinElA-mediated cell growth control mechanisms.