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Growth factor-induced delayed early response genes
A Lanahan1, J B Williams, L K Sanders
1Howard Hughes Medical Institute, Baltimore, Maryland.
Abstract:
Growth factors induce the sequential expression of cellular genes whose products are thought to mediate long-term responses to the growth factors. In mouse 3T3 fibroblastic cells, the first genes to be expressed (immediate-early genes) are activated within minutes after the addition of platelet-derived growth factor, fibroblast growth factor, or serum. By cDNA cloning, we have identified genes that are activated after a delay of a few hours and several hours prior to serum-induced DNA replication. Activation of these delayed early response genes requires new protein synthesis, presumably the synthesis of immediate-early transcription factors described previously. Partial or complete sequencing of 13 different delayed early cDNAs, representing about 40% of the 650 primary cDNA isolates, revealed that 8 were related to known gene sequences and 5 were not. Among the former are cDNAs encoding nonhistone chromosomal proteins [HMGI(Y) and HMGI-C], adenine phosphoribosyltransferase (APRT), a protein related to human macrophage migration inhibitory factor (MIF), a protein of the major intrinsic protein (MIP) family homologous to the integral membrane protein of human erythrocytes, and cyclin CYL1. In 3T3 cells, the delayed early gene response to growth factors appears to be at least as complex as the immediate-early gene response previously described.
Insights
Researchers identified delayed early response genes in mouse 3T3 cells crucial for growth factor-induced DNA replication. These genes, activated after new protein synthesis, indicate a complex cellular response to growth factors.
Area of Science:
- Cellular and Molecular Biology
- Gene Regulation
- Signal Transduction
Background:
- Growth factors trigger sequential gene expression for long-term cellular responses.
- Immediate-early genes are rapidly activated by growth factors within minutes.
- Understanding delayed gene responses is key to deciphering growth factor signaling pathways.
Purpose of the Study:
- To identify and characterize delayed early response genes activated hours before DNA replication.
- To investigate the protein synthesis requirement for delayed early gene activation.
- To analyze the novelty and known relationships of these delayed early genes.
Main Methods:
- cDNA cloning to isolate genes activated after a delay.
- Partial or complete sequencing of identified delayed early cDNAs.
- Analysis of gene sequence homology to known sequences.
Main Results:
- Identified genes activated hours before serum-induced DNA replication in 3T3 cells.
- Confirmed that delayed early gene activation requires new protein synthesis.
- Sequencing revealed 8 known gene-related sequences and 5 novel sequences, including those for HMGI(Y), HMGI-C, APRT, MIF-related protein, MIP family protein, and cyclin CYL1.
Conclusions:
- The delayed early gene response to growth factors in 3T3 cells is complex.
- These delayed genes play a role in mediating long-term cellular responses to growth factors.
- The findings expand our understanding of the intricate gene regulatory networks governing cell proliferation.