The Max transcription factor network: involvement of XXXX in differentiation and an approach to identification of target genes.

@entity517 @entity29243 @entity9613
The small bHLHZip protein, Max, was originally identified through its interaction with @entity517 family proteins and appears to be an obligate partner for @entity517 function. Max has now been found to interact with at least two other proteins, @entity9613 and @entity29243 . These also belong to the bHLHZip class but are otherwise unrelated to @entity517 . @entity9613 has been shown to abrogate the positive transcriptional activity of @entity517 and to inhibit @entity517 in co-transformation assays. This suggests that @entity9613 may antagonize @entity517 function. @entity9613 is rapidly induced upon differentiation, a time when @entity517 is frequently down-regulated. We show here evidence for @entity9613 expression upon differentiation of myeloblasts, monoblasts, and keratinocytes. @entity9613 :Max complexes are detected during differentiation and appear to replace the @entity517 :Max complexes present in proliferating cell populations. Since these complexes appear to form even in the presence of @entity517 , there may exist mechanisms that act to inhibit @entity517 :Max, or to promote @entity9613 :Max, complex formation. We speculate that Max complex switching causes a change in the transcriptional activity of groups of target genes. @entity9613 is not induced in all differentiating cell types, suggesting that other, possibly tissue-restricted, proteins might act in similar switch mechanisms to effect changes in transcriptional programs. We have also developed an approach to identification of the gene targets for @entity517 :Max complexes. By employing an immunoisolation procedure, we have begun characterization of several clones whose expression levels correlate with those of @entity517 . Further identification of @entity517 -regulated genes may allow us to determine the molecular mechanism by which @entity517 governs cell proliferation and differentiation.
