Axin is a recently identified protein encoded by the fused locus in mice that is required for normal vertebrate axis formation. We have defined a 25-amino-acid sequence in axin that comprises the glycogen synthase kinase 3␤ (GSK-3␤) interaction domain (GID). In contrast to full-length axin, which has been shown to antagonize Wnt signaling, the GID inhibits GSK-3␤ in vivo and activates Wnt signaling. Similarly, mutants of axin lacking key regulatory domains such as the RGS domain, which is required for interaction with the adenomatous polyposis coli protein, bind and inhibit GSK-3␤ in vivo, suggesting that these domains are critical for proper regulation of GSK-3␤ activity. We have identified a novel self-interaction domain in axin and have shown that formation of an axin regulatory complex in vivo is critical for axis formation and GSK-3␤ activity. Based on these data, we propose that the axin complex may directly regulate GSK-3␤ enzymatic activity in vivo. These observations also demonstrate that alternative inhibitors of GSK-3␤ can mimic the effect of lithium in developing Xenopus embryos.

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The traditional list of etiological factors related to oral squamous cell carcinoma namely, tobacco, alcohol, syphilis, and oral sepsis has been expanded to include iron deficiency, chronic candidosis, and herpes simplex virus. The development of current concepts in these areas is discussed. In evaluating the need for future research, special emphasis is given to the concepts of multifactorial etiology and the role of mutagens. Suggestions for future research are discussed.

A standardized continuing education course was developed to determine if behavior in dental practices could be modified to improve office participation in oral and pharyngeal cancer control through early detection and tobacco-use cessation.