Isolation and characterization of two novel metalloproteinase genes linked to the Cdc2L locus on human chromosome 1p36.3.
The terminal end of the short arm of human chromosome 1, 1p36.3, is frequently deleted in a number of tumors and is believed to be the location of multiple tumor suppressor genes. Thus far, a bona fide tumor suppressor gene from this region has not been identified. The isolation and characterization of new 1p36 genes is, therefore, of some interest. Two novel matrix metalloproteinase genes, MMP21 and MMP22, have been identified in the Cdc2L1-2 locus, which spans approximately 120 kb on 1p36.3. These genes encode novel metalloproteinases that contain prepro, catalytic, cysteine-rich, interleukin-1 receptor-related, and proline-rich domains. Their catalytic domains are most closely related to stromelysin-3 and contain the consensus HEXXH zinc-binding region required for enzyme activation, while their cysteine-rich domains appear to be related to a number of human, mouse, and Caenorhabditis elegans metalloproteinase sequences. Of some possible interest is the absence of a highly conserved cysteine residue in the proenzyme domain, the so-called "cysteine switch," which has been shown to be involved in the autocatalytic activation of many metalloproteinases. The MMP genes are located less than 1 kb from the 3' regions of Cdc2L1 and Cdc2L2, suggesting that the MMP and Cdc2L genes are part of a larger region that has been duplicated. Finally, the MMP21/22 genes express multiple mRNAs, some of which are derived by alternative splicing, in a tissue-specific manner.
Gururajan
R
R
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee, 38101, USA.
Grenet
J
J
Lahti
J M
JM
Kidd
V J
VJ
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012313:RNA / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D012313:RNA; D008666:Metalloendopeptidases