Characterization of the human p57KIP2 gene: alternative splicing, insertion/deletion polymorphisms in VNTR sequences in the coding region, and mutational analysis.
We have isolated human cDNA and genomic clones of a gene termed p57KIP2, which is related to the p2I WAFI and p27 KIP1 genes that encode inducible inhibitors of cyclin-dependent kinase activity. The p57 gene contains three GC-rich introns of 166 bp, 566 bp, and 83 bp, and two of the four exons correspond to coding regions. Alternative splicing generates the heterogeneity in the translational initiations. As this gene has been localized to chromosomal band 11pI5.5, a region thought to be the location of a tumor suppressor gene(s) for carcinomas of the breast, bladder, and liver, we have examined a large number of tumors for genetic alterations of p57. Although no somatic mutation has been detected, we have found several normal variations in this gene, including four types of 12-bp in-frame deletions in the proline/alanine repeating domain, in which nearly 40 motifs, viz., 5'-CCGGCC-3', are tandemly repeated.
Tokino
T
T
Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Japan.
Urano
T
T
Furuhata
T
T
Matsushima
M
M
Miyatsu
T
T
Sasaki
S
S
Nakamura
Y
Y
D017398:Alternative Splicing; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004251:DNA Transposable Elements; D004791:Enzyme Inhibitors; D005091:Exons; D005260:Female; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014176:Protein Biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D001749:Urinary Bladder Neoplasms / Q000235:genetics
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D017931:DNA Primers; D004251:DNA Transposable Elements; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D018844:Cyclin-Dependent Kinases