IDENTIFICATION OF CASEIN KINASE-II PHOSPHORYLATION SITES IN MAX - EFFECTS ON DNA-BINDING KINETICS OF MAX HOMODIMER AND MYC MAX HETERODIMERS/

Myc proteins have been implicated in the regulation of cell growth and differentiation. The identification of Max, a basic region/helix-loop -helix/leucine zipper protein, as a partner for Myc has provided insig hts into Myc's molecular function as a transcription factor. Recent ev idence indicates that the relative abundance of Myc and Max is importa nt to determine the level of specific gene transcription; In this repo rt we have identified two major in vivo phosphorylation sites in Max ( Ser-2 and -11) which can be modified in vitro by casein kinase II (CKI I). Phosphorylation of these sites modulates DNA-binding by increasing both the on- and off-rates of Max homo- as well as Myc/Max heterodime rs. In addition, our data indicate that the steady state binding of th e shorter version of Max (p21) to DNA was similar yet its rate of diss ociation faster than that of the longer version of Max (p22). These da ta argue that different Max complexes have different kinetic propertie s and that these can be modified by CKII phosphorylation. We propose t his as an important biological mechanism by which different dimeric co mplexes can exchange with varying efficiencies on DNA, thereby respond ing to changes in cell growth conditions.