E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.
The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation. Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130. In vivo, pRb is found in complex with a subset of E2F components--namely, E2F-1, E2F-2, and E2F-3. Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to interact with p130 in a yeast two-hybrid system. E2F-4 and -5 share common sequences with E2F-1, E2F-2, and E2F-3 and, like these other E2Fs, the ability to heterodimerize with DP-1, thereby acquiring the ability to bind an E2F DNA recognition sequence with high affinity. However, in contrast to E2F-1, E2F-4 and E2F-5 fail to bind pRb in a two-hybrid assay. Moreover, they show a unique pattern of expression in synchronized human keratinocytes: E2F-4 and E2F-5 mRNA expression is maximal in mid-G1 phase before E2F-1 expression is detectable. These findings suggest that E2F-4 and E2F-5 may contribute to the regulation of early G1 events including the G0/G1 transition.
Sardet
C
C
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Vidal
M
M
Cobrinik
D
D
Geng
Y
Y
Onufryk
C
C
Chen
A
A
Weinberg
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002453:Cell Cycle; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; D005347:Fibroblasts; D015870:Gene Expression; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; C092558:E2F5 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors