Elk3 from hamster--a ternary complex factor with strong transcriptional repressor activity.
Elk3 belongs to the Ets family of transcription factors, which are regulated by the Ras/mitogen-activated protein kinase-signaling pathway. In the absence of Ras, this protein is a strong inhibitor of transcription and may be directly involved in regulation of growth by downregulating the transcription of genes that are activated during entry into G1. We have isolated the Cricetulus griseus Elk3 gene from the Chinese hamster ovary (CHO) cell line and investigated the transcriptional potential of this factor. Transient transfections revealed that, in addition to its regulation of the c-fos promoter, Elk3 from CHO cells seems to inhibit other promoters controlling expression of proteins involved in G1/S phase progression; Cyclin D1 and DHFR. As has been described for the Elk3 homologs Net (Mouse) and Sap-2 (Human), the results of the present study further indicate that hamster Elk3 is a target of the Ras-Raf-MAPK pathway, and cotransfections with constitutively active H-ras relieves its negative transcriptional activity. No cells stably expressing exogenous Elk3 could be obtained, possibly due to an unspecified toxic or growth retarding effect. These findings support a possible role for Elk3 in growth regulation and reveal a high degree of homology for this protein across species.
Hjortoe
Gertrud Malene
GM
Department Molecular Cell Biology, Institute of Molecular Biology, University of Copenhagen, Copenhagen, Denmark.
Weilguny
Dietmar
D
Willumsen
Berthe Marie
BM
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D017930:Genes, Reporter / Q000235:genetics; D016762:Genes, fos / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D016415:Sequence Alignment; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D019938:Cyclin D1; D013762:Tetrahydrofolate Dehydrogenase