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General Comment |
The matrix metalloproteinases are secreted glycoproteins that are involved in the remodeling of the extracellular matrix. Gururajan et al. (1998) identified 2 novel matrix metalloproteinase genes, MMP23A, which they called MMP21, and
MMP23B , which they called MMP22. The nucleotide sequences of MMP21 and MMP22 are nearly identical.
Using a combination of techniques, the authors isolated cDNAs corresponding to alternatively spliced transcripts that
encode 3 protein isoforms, MMP21/22A, MMP21/22B, and MMP21/22C. The MMP21 and MMP22 proteins contain
prepro-, catalytic, cysteine-rich, IL1 receptor-related, and proline-rich domains. Both genes contain 8 exons, and the
exons generally correspond to the structural domains of the putative protein products. Northern blot analysis revealed
that a 1.4-kb MMP21/22 transcript was expressed in heart, placenta, ovary, testis, and prostate. A 0.8-kb mRNA was
detected in heart and pancreas, and an additional 2.4-kb mRNA was detected in ovary.
NCBI Summary:
Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene lacks the signal sequence found in other MMPs, suggesting that it may function intracellularly. The substrate for the enzyme has not been identified, but it is thought that the protein may play a role in reproductive processes. This gene, MMP23A, is part of a duplicated region of chromosome 1p36.3, which includes a second gene, MMP23B, which is almost identical. This gene was previously named MMP21 but the current name is MMP23A. Transcript variants for this gene have been described, but their full length sequences have not been determined.
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Comment |
Junji Ohnishi, et al 2001 reported the Cloning and Characterization of a Rat Ortholog of MMP-23 (Matrix Metalloproteinase-23), a Unique Type of Membrane-Anchored Matrix Metalloproteinase and Conditioned Switching of Its Expression during the
Ovarian Follicular Development.
Transient expression of epitope-tagged rat and human MMP-23 in COS-1 cells revealed that the enzymes were synthesized as a
membrane-anchored glycoprotein with type II topology. Indirect immunofluorescent analysis showed that subcellular
localization of MMP-23 was predominantly in the perinuclear regions. The transfected human MMP-23 protein was
processed endogenously to the soluble form in COS-1 cells.
Notably, in situ
hybridization analysis revealed a dramatic switching of MMP-23 mRNA localization from granulosa cells to
theca-externa/fibroblasts and ovarian surface epithelium during the follicular development. In serum-free primary
culture of rat granulosa cells, a drastic diminution of MMP-23 mRNA expression was observed in response to FSH
action between 24 h and 48 h of culture. The observed effect of FSH on MMP-23 expression was mimicked by
treatment of granulosa cells with forskolin or 8-bromo (Br)-cAMP. In contrast, MMP-23 mRNA levels increased in
theca-interstitial cells regardless of the presence of LH in the culture. However, treatment of theca-interstitial cells with
forskolin or 8-Br-cAMP markedly reduced the expression of MMP-23 with a concomitant increase in progesterone
production. These results indicate that the MMP-23 gene is spatially and temporally regulated in a cell type-specific
manner in ovary via the cAMP signaling pathway.
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