In RATlA fibroblasts, expression of the prothymosin a gene is under the transcriptional control of the c-myc proto-oncogene. We have now cloned the rat gene encoding prothymosin a and show that the cloned gene is regulated by c-myc The c-myc proto-oncogene was discovered as the cellular homolog of the transforming gene of the chicken myelocytomatosis virus MC29 (16, 63). c-myc appears to act as a key regulator of cell proliferation; this notion is supported by the demonstration that expression of c-myc closely correlates with cell proliferation (23,34,40,45,66,67) and that cells expressing c-myc under the control of constitutive promoter lose the ability to control proliferation in response to growth factors and often undergo apoptosis when deprived of them (29, 39).c-myc encodes two nuclear phosphoproteins (1, 21, 48) that carry a number of structural and functional elements characteristic of transcription factors. The Myc protein contains both a helix-loop-helix (46) and a leucine zipper (42) motif, both of which are essential for the transforming properties of the protein (18, 59). The Myc protein binds to DNA and specifically recognizes CA(C/T)GTG sequences (termed E boxes) (11,50). Both in vitro and in vivo, Myc heterodimerizes with a second helix-loop-helix protein, termed Max (12,13,49,65). Dimerization with Max enhances the affinity of Myc to DNA and is a prerequisite for both transcriptional activation and transformation by c-myc (2,3,41). In the absence of Myc, Max forms homodimers that also recognize E-box sequences (9,12,37,49) and, in contrast to Myc/Max heterodimers, repress transcription from synthetic reporter constructs that carry E boxes in their promoters (4,33,41,51). In contrast to c-myc, Max is also expressed in quiescent cells (9,13,49); the relative levels of c-myc and Max therefore provide a model of how growth regulation of E-box-containing promoters might be achieved. Further proteins that heterodimerize with either Max (5, 69) or Myc (53,54,57) have been isolated and may affect gene regulation by c-myc.
