Isolation and characterization of a chicken homolog of the E2F-1 transcription factor.
In higher eukaryotes, the E2F-1 transcription factor is an essential and limiting component of cell cycle progression in late G1. E2F-1 heterodimerizes with members of the DP gene family and the resulting heterodimer regulates the expression of several proto-oncogenes and the genetic machinery of DNA replication. Cell cycle regulation of E2F activity is mediated through its association with the tumor suppressor Rb gene product. To examine the evolutionary conservation of the E2F-1 protein sequence and its developmental expression pattern we have isolated and sequenced the chick E2F-1 gene (chE2F-1) cDNA. The chicken protein is 34 amino acids (a.a) shorter than its human counterpart (403/437 a.a.) but has extremely well conserved bHLH and pRb binding domains, with respectively 94% and 83% identity. The position of the leucine zipper is also strictly conserved thereby accounting for ability of E2F-1 to form heterodimers with human and chicken DP-1. E2F-1 expression was analysed in synchronized cells as well as in embryonic or newborn chick tissues and appears to be closely correlated to the cell proliferation rate. In situ hybridization studies have shown very high expression levels in the neuroretina during the early stages of embryonic development when active neuroblast division occurs. In contrast, a sharp down-regulation is observed when cells become postmitotic. Overexpression of the chE2F-1 protein leads to oncogenic transformation only when a truncated version of the transgene lacking the pRb binding domain is used; the full length protein either has no effect or may be deleterious for cell survival.
D017502:Adenovirus E2 Proteins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D005796:Genes; D006801:Humans; D017403:In Situ Hybridization; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000196:embryology; D056465:Retinoblastoma-Binding Protein 1; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
D017502:Adenovirus E2 Proteins; C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D046911:Macromolecular Substances; D012333:RNA, Messenger; D056465:Retinoblastoma-Binding Protein 1; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors