細胞初期生長基因的轉錄調空機制與其啟動子上的反應核酸序列有密切的
關係。 血清反應因子是一個分子量為六十七千道耳吞的磷酸化蛋白質,以
雙複合體的形式結合在血清反應核酸序列之上我們發現血清反應因子的C
端可以被去氧核醣核酸磷酸化酵素所磷酸化。它主要作用的位置是在血清
反應因子C端的絲氨酸435與絲氨酸446,而其後緊接的麩酸醯氨則對受質的
認識作用十分重要。我們同時也發現磷酸化的二個絲氨酸,正好位於血清
反應因子負責轉錄作用的部位。當我們將此二個氨基酸突變成班氨基初油
酸之後,很明顯的轉錄活性受到影響。血清反應因子也具有醣化的現象,因
此可用小麥胚芽凝集素膠體層析管柱加以純化。我們觀察到有一些同樣對
血清反應核酸序列具有親和性的較小分子量的蛋白質複合體,卻並不具有
此一現象。利用核酸競爭試驗,我們發現其中二個可能是YY1及NFkB。YY1
在其他實驗室的報告中已知具有抑制作用;而我們經實驗證明,NFkB對血清
反應核酸序列啟動轉錄作用的功能也會發生抑制的效果。另外,我們也找
到了一個對血清反應因子具有親和性的蛋白質,屬於ETS腫瘤基因族群。

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.

感言
目錄
摘要
緒論
Part I
Part II
figures
References