ABERRANT CELL-GROWTH INDUCED BY AVIAN WINGED HELIX PROTEINS

Winged helix transcription factors act as important regulators of embr yonal development and tissue differentiation in vertebrates and invert ebrates. Identification of the retroviral oncogene v-qin as a member o f the winged helix family showed that these developmental regulators a lso have oncogenic potential. We used low-stringency hybridization of a chicken embryonic cDNA library to isolate cDNA clones coding for thr ee chicken winged helix (CWH) proteins, CWH-1, CWH-2, and CWH-3. The C WH genes are transcribed in a tissue-restricted pattern in adult and e mbryonic chicken tissues, The CWH proteins bind to conserved DNA bindi ng sites for winged helix proteins in a sequence-specific manner. Expr ession of the CWH proteins from replication-competent retroviral RCAS vectors induces changes in morphology and growth pattern of chicken em bryo fibroblasts. CWH-1 and CWH-3 also induce anchorage-independent gr owth in agar. Chicken embryo fibroblasts expressing the RCAS construct s release replication-competent viruses that are able to elicit the sa me cellular changes as the parental plasmid DNA. Our results suggest t hat winged helix transcription factors not only function as regulators of development and differentiation but also have the potential to sti mulate abnormal cell proliferation.