PFM1 (PRDM4), a new member of the PR-domain family, maps to a tumor suppressor locus on human chromosome 12q23-q24.1

The PR domain, first noted as the PRDI-BF1 (HGMW-approved symbol PRDM1) and RIZ (HGMW-approved symbol PRDM2) homologous region, defines a small family of transcription factors involved in cell differentiation and tumorigenesi s. The shared role of this family in human cancer raises considerable inter est in identifying novel members of this family as candidate cancer genes. This paper describes a new human PR family member, designated PFM1 (HGMW-ap proved symbol PRDM4). A full-length PFM1 cDNA of 3902 nucleotides has been isolated based on its homology to the PR domain. It encodes an open reading frame of 796 amino acids and contains a PR domain in the middle region and six zinc finger motifs at the carboxyl-terminus. Several PFM1 mRNA species of different lengths were detected by Northern blot analysis, one species of which lacked the amino-terminal region of PFM1 and part of the PR domain . The major PFM1 mRNA species of similar to 4.6 kb was widely expressed but more abundant in ovary, testis, pancreas, brain, heart, and prostate. PFM1 mRNA levels were highly elevated in PC12 cells treated with NGF, suggestin g a role for PFM1 in the NGF signal transduction pathway. STS marker and ra diation hybrid analyses mapped PFM1 to human chromosome 12q23-q24.1, a regi on thought to harbor tumor suppressor genes for ovarian, gastric, and pancr eatic cancers. These results suggest a role for PFM1 in cell differentiatio n and tumor suppression, remarkably consistent with the known functions of the PR-domain family. (C) 1999 Academic Press.