Human Serum Response Factor: Post-translational Modifications and Protein Complex Formation

• Main Authors: Liu Shu-Hui, 劉淑惠
• Other Authors: Ng Sun-Yu, Liu Ying-Chang
• Format: Others
• Language: zh-TW
• Published: 1993
• Online Access: http://ndltd.ncl.edu.tw/handle/65652964083629556208

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.