p21B, a variant of p21(Waf1/Cip1), is induced by the p53 family.
Alternative splicing or expression from an alternate promoter can produce variants of a gene. To determine whether the p21(Waf1/Cip1) locus is regulated by these mechanisms, we searched for and found two transcripts, p21B and p21C, that are expressed from an alternate promoter in the first intron of the p21 gene. While p21C encodes the p21 cyclin-dependent kinase inhibitor, p21B encodes a novel protein and the transcript is ubiquitously expressed in 16 human tissues tested. Like p21, both p21B and p21C are induced by DNA damage, p53, and other p53 family members through a proximal p53 response element in the promoter of p21B and p21C. However, unlike p21, which induces cell cycle arrest, we found that overexpression of p21B induces apoptosis. These findings indicate that the p21 locus expresses at least two structurally distinct, but functionally related, variants of the p21 gene from discrete promoters.
Nozell
Susan
S
Department of Cell Biology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Chen
Xinbin
X
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D002166:Camptothecin