Interest in the Ets proteins has grown enormously over the last decade. The v‐ets oncogene was originally discovered as part of a fusion protein expressed by a transforming retrovirus (avian E26), and later shown to be transduced from a ceilular gene. About 30 related proteins have now been found in species ranging from flies to humans, that resemble the vEts protein in the so‐called ‘ets domain’. The ets domain has been shown to be a DNA‐binding domain, that specifically interacts with sequences containing the common core trinucleotide GGA. Furthermore, it is involved in protein–protein interactions with co‐factors that help determine its biological activity. Many of the Ets‐related proteins have been shown to be transcription activators, like other nuclear oncoproteins and anti‐oncoproteins (Jun, Fos, Myb, Myc, Rel, p53, etc.). However, Ets‐like proteins may have other functions, such as in DNA replication and a general role in transcription activation. Ets proteins have been implicated in regulation of gene expression during a variety of biological processes, including growth control, transformation, T‐cell activation, and developmental programs in many organisms. Signals regulating cell growth are transmitted from outside the cell to the nucleus by growth factors and their receptors, G‐proteins, kinases and transcription factors. We will discuss how several Ets‐related proteins fit into this scheme, and how their activity is regulated both post‐and pre‐translationally. Loss of normal control is often associated with conversion to an onco‐protein. vEts has been shown to have different properties from its progenitor, which might explain how it has become oncogenic. Oncogene‐related products have been implicated in the control of various developmental processes. Evidence is accumulating for a role for Ets family members in Drosophila development, Xenopus oocyte maturation, lymphocyte differentiation, and viral infectious cycles. An ultimate hope in studying transformation by oncoproteins is to understand how cells become cancerous in humans, which would lead to more effective treatments. vEts induces erythroblastosis in chicken. Cellular Ets‐family proteins can be activated by proviral insertion in mice and, most interestingly, by chromosome translocation in humans. We are at the beginning of understanding the multiple facets of regulation of Ets activity. Future work on the Ets family promises to provide important insights into both normal control of growth and differentiation, and deregulation in illness.

Ras signaling appears to be mediated in part by transcription factors that belong to the ets gene family. To identify downstream targets for the Ras signal transduction pathway, we have used Ras-transformed mouse fibroblasts to isolate a new member of the ets gene family, net. Net has sequence similarity in three regions with the ets factors Elkl and SAP1, which have been implicated in the serum response of the fos promoter. Net shares various properties with these proteins, including the ability to bind to ets DNA motifs through the Ets domain of the protein and form ternary complexes with the serum response factor SRF on the fos serum response element, SRE. However, Net differs from Elkl and SAP1 in a number of ways. The pattern of net RNA expression in adult mouse tissues is different. Net has negative effects on transcription in a number of assays, unlike Elkl. Strikingly, Ras, Src, and Mos expression switch Net activity to positive. The study of Net should help in understanding the interplay between Net and other members of the Elk subfamily and their contribution to signal transduction through Ras to the nucleus.

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