| Summary: | 博士 === 國立清華大學 === 生命科學研究所 === 81 === Transcriptional Indution of the proto-oncogene c-fos and other
Serum Response element (SRE)-dependent immediate-early genes in
response to growth factors and other mitogenic signals is pre-
sumed to be mediated by the Serum Response Factor (SRF) and its
associated proteins. The carboxyl-terminal domain of human SRF
is phosphorylated in vivo and is recognized by a double-
stranded DNA-activated serine/threonine specific protein
kinase, DNA-PK. SRF phosphorylation by DNA-PK was stimulated by
its cognate bind -ing site. The DNA-PK phosphorylation sites
have been mapped to Sre435 and Ser446 in the C-terminal region,
both serines are followed by glutamine. Chaning Gln-436 and
Gln-447to other re- duced or eliminated phosphorylation by DNA-
PK. The carboxyl- terminal transactivation domain of SRF was
mapped within a 71- amino-acid region that contains these two
DNA-PK phosphorylation sites. Amino acid substitutions which
interfere with the phos- phorylation at Ser435/446 suggest that
phosphorylation of these sites may modulate SRF activity in
vivo. SRF is O-glycosylated on multiple serine and/or
threonine residues, but the low-mole- cular weight SRE binding
complexes previously found in mouse em- bryos are not O-
glycosylated. Two of these smaller complexes appeared to
contain the YY1 repressor and NF-kB related factors.
Cotransfection of NF-kBp65 reduced the c-fos SRE dependent pro-
moter activity presumbly through inhibition of the SRF transac-
tivation function. Besides these two factors, the PEA3 binding
factor, an ETS domain containing protein, was found to bind SRF.
|
|---|
