New light on Myc and Myb. Part I. Myc.

The group of proto-oncogenes found to encode nuclear proteins now includes myc, myb, fos, jun, ski, cbl, eibA, members of the ets family^ and possibly several others. Given that so many cytoplasmic and membrane-associated oncoproteins are involved in signal transduction pathways, one rather appealing notion has been that some or all of the nuclear oncoproteins encoded by these genes might act to mediate specific transcriptional responses to signals originally generated in the plasma membrane or cytoplasm (for review, see Weinberg 1989). During the last several years, a number of these oncoproteins, including ErbA, Fos, Jun and, most recently, Ets, have been demonstrated to be directly involved in transcriptional regulation. It is somewhat ironic that Myc and Myb, two of the first oncoproteins to be shown localized to the nucleus, have appeared to elude functional characterization. However, recent evidence has demonstrated that Myb also functions in transcription and, while Myc has remained a citadel of incomprehensibility, new studies have begun to bring this mysterious protein into sharper focus. At first glance, Myc and Myb would appear to have little in common, aside from the fact that both are predominantly localized in the nucleus. They are quite different structurally and their patterns of expression are also rather distinct, with Myc present in nearly all cell types while Myb is restricted to hematopoietic cells. However, the functions of both of these oncoproteins appear to be linked to proliferation, and these oncoproteins clearly play major roles in cell differentiation. Furthermore, recent work has cast some new light on both oncoproteins, and in what follows we attempt to meld older with more recent evidence relating to possible functions. This review will appear in two segments. In part I we consider studies relating to the structure and potential function of Myc; part II, to appear in the next issue, will discuss recent findings on Myb.