Genomic structure, expression and mutational analysis of the P15 (MTS2) gene.
The P15 gene (MTS2) encodes a cyclin-dependent kinase (CDK) inhibitor with considerable sequence identity and biochemical similarity to the CDK inhibitor p16. It is closely linked to the P16 gene (MTS1) and is homozygously deleted in many tumor cell lines. These features suggest that p15 may be a tumor suppressor. We have determined the genomic structure of P15 and examined its pattern of mRNA expression. In addition, we have shown that ectopic expression of p15 inhibits growth of tumor-derived cell lines. We have also searched for P15 mutations in tumor cell lines and in 9p21-linked melanoma kindreds. Other than the previously described homozygous deletions, no mutations of P15 were found. Collectively, these observations suggest a role for p15 in growth regulation, but a limited role for p15 in tumor progression.
Stone
S
S
Myriad Genetics, Inc., Salt Lake City, Utah 84018, USA.
Dayananth
P
P
Jiang
P
P
Weaver-Feldhaus
J M
JM
Tavtigian
S V
SV
Cannon-Albright
L
L
Kamb
A
A
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006801:Humans; D008545:Melanoma / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins