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A growth factor-inducible gene encodes a novel nuclear protein with zinc finger structure
J A Fernandez-Pol1, D J Klos, P D Hamilton
1Laboratory of Molecular Oncology, DVA Medical Center, St. Louis, Missouri 63106.
Abstract:
Growth factors rapidly induce numerous genes that encode regulatory proteins, many of which have been identified by cDNA cloning. In this study, differential hybridization was used to screen a cDNA library constructed from human mammary carcinoma MDA-468 cells that were stimulated with transforming growth factor beta-1 (TGF-beta 1) in the presence of cycloheximide. One of the cDNA clones that was induced by TGF-beta 1 was found to have a nucleotide sequence that predicts a 9,450-Da protein with homology to regulatory DNA-binding proteins. This clone was designated metallopan-stimulin-1 (MPS-1) because it encodes a metalloprotein whose mRNA is expressed in a wide variety of actively proliferating cells and tumor tissues. MPS-1 protein contains one "zinc finger" domain of the C4 type, similar to those present in proteins of the steroid/thyroid hormone receptor superfamily and other DNA-binding proteins. The mRNA for MPS-1 was induced in MDA-468 cells by fetal calf serum, TGF-beta 1, TGF-beta 2, and cAMP analogues. The MPS-1 gene is expressed at relatively high levels in several human carcinoma cell lines, particularly those derived from ectodermal layers, and at higher levels in melanomas (ontogenically of neural origin). In contrast, the MPS-1 mRNA is expressed at low levels in normal WI-38 human lung diploid fibroblasts in culture. We hypothesize that MPS-1 protein may play a role as a potentially important mediator of cellular proliferative responses to various growth factors and other environmental signals.
Insights
Researchers identified metallopan-stimulin-1 (MPS-1), a novel protein induced by growth factors. MPS-1, a DNA-binding protein, may mediate cellular proliferation in response to various signals.
Area of Science:
- Molecular Biology
- Cell Biology
- Genomics
Background:
- Growth factors regulate gene expression, often involving regulatory proteins identified via cDNA cloning.
- Understanding these induced genes is crucial for deciphering cellular responses to external stimuli.
Purpose of the Study:
- To identify novel genes induced by transforming growth factor beta-1 (TGF-beta 1) in human mammary carcinoma cells.
- To characterize the function and expression of a newly identified TGF-beta 1-induced gene.
Main Methods:
- Differential hybridization was employed to screen a cDNA library from TGF-beta 1-stimulated MDA-468 cells.
- Nucleotide sequencing was used to predict protein structure and homology.
- Quantitative analysis of mRNA expression in various cell lines.
Main Results:
- A novel cDNA clone, metallopan-stimulin-1 (MPS-1), was identified and induced by TGF-beta 1.
- MPS-1 encodes a 9,450-Da protein with a zinc finger domain, suggesting DNA-binding activity.
- MPS-1 mRNA was upregulated by various growth factors and signaling molecules in carcinoma cell lines, especially melanomas, but low in normal fibroblasts.
Conclusions:
- MPS-1 is a metalloprotein potentially involved in mediating cellular proliferation.
- Its expression pattern suggests a role in cancer development, particularly in tumors of ectodermal origin.
- Further research is warranted to elucidate the precise role of MPS-1 in growth factor signaling and cancer.