IDENTIFICATION AND CHARACTERIZATION OF A NOVEL SQUAMOUS CELL-ASSOCIATED GENE-RELATED TO PMP22

In this study, we identify and characterize a novel gene, CL-20, that encodes a 17.8-kDa protein with sequence and structural similarity to the growth arrest specific gene gas3/peripheral myelin protein gene PM P22. The CL-20 protein exhibits a 43% identity with PMP22. The positio ns of the four lipophilic domains and the N-glycosylation site of PMP2 2 are conserved in CL-20, suggesting that it also is an integral membr ane glycoprotein. The CL-20 gene is located on human chromosome 12 rat her than 17 and encodes a 2.8-kilobase mRNA instead of 1.7-kilobase mR NA. These observations indicate that the CL-20 gene is related to but distinct from PMP22. In contrast to PMP22, CL-20 mRNA and protein are induced during squamous differentiation of rabbit tracheal epithelial cells in vitro, and Northern blot analysis and in situ hybridization d emonstrated that CL-20 mRNA is most abundant in squamous epithelia. Th ese results indicate that the high expression of CL-20 is closely corr elated with squamous differentiation. The differences in tissue-specif ic expression and regulation between CL-20 and PMP22 suggest different roles for these two proteins. Retinoids, which inhibit squamous diffe rentiation, repress the induction of CL-20. The retinoic acid receptor selective retinoid SRI-6751-84 is the most effective in suppressing C L-20, suggesting that the activation of the retinoic acid receptor sig naling pathway is important in this suppression.