PARP1 ADP-ribosylates SMAD3 and SMAD4
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PARP1 ADP-ribosylates SMAD3 and SMAD4 in SMAD2/3:SMAD4 heterotrimer. ADP-ribosyl group is attached to glutamic acid residues E50 and E52 of SMAD3 and unknown amino acid residues of SMAD4. ADP-ribose monomer attached to SMAD3 and SMAD4 is subsequently extended to poly (ADP-ribosyl) chains (i.e. PAR chains) by PARP1, which is not shown here. ADP-ribosylation (PARylation) of SMAD3 and SMAD4 by PARP1 inhibits binding of SMAD2/3:SMAD4 heterotrimers to SMAD binding elements (SBEs) in promoters of SMAD-target genes.
PARP1 通过ADP-核糖基化作用修饰SMAD2/3:SMAD4异源三聚体中的SMAD3和SMAD4。ADP-核糖基团连接至SMAD3的谷氨酸残基E50和E52,以及SMAD4中未知的氨基酸残基。连接至SMAD3和SMAD4的ADP-核糖单体随后被PARP1扩展为多(ADP-核糖基)链(即PAR链),此处未展示。PARP1对SMAD3和SMAD4的ADP-核糖基化(PAR化)作用抑制了SMAD2/3:SMAD4异源三聚体与SMAD靶基因启动子中的SMAD结合元件(SBEs)的结合。
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