The D-domain of Sp3 modulates its protein levels and activation of the p21(CIP1/WAF1) promoter.
A variety of signals result in the transcriptional induction of the p21(CIP1/WAF1) promoter and both Sp1 and the related Sp3 proteins have been implicated in this induction. We have characterized the role of the C-terminal D-domains of both Sp1 and Sp3 proteins in the activation of this promoter in response to butyrate treatment of Hep G2 cells. We have defined a negative regulatory domain present in the C-terminus of Sp3. This domain decreases Sp3 protein levels, and this property can be transferred to Sp1. Changes in Sp3 protein levels may bring about growth arrest through the induction of inhibitors of the cell cycle such as p21(CIP1/WAF1).
Hammill
Deborah
D
Queen's Cancer Research Institute, Department of Biochemistry and Pathology, Queen's University, Kingston, Ont., Canada.
Jain
Nidhi
N
Armstrong
Susan
S
Mueller
Christopher R
CR
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor