Alternative titles; symbolsO(6)-METHYLGUANINE-INDUCED APOPTOSIS 2; MAPO2CHROMOSOME 1 OPEN READING FRAME 201; C1ORF201HGNC Approved Gene Symbol: STPG1Cytogenetic ...
Alternative titles; symbols
HGNC Approved Gene Symbol: STPG1
Cytogenetic location: 1p36.11 Genomic coordinates (GRCh38): 1:24,356,998-24,415,532 (from NCBI)
O(6)-methylated guanine in DNA is mutagenic due to mispairing of O(6)-methylguanine with thymine during replication, leading to GC-to-AT transitions. The methyltransferase MGMT (156569) can repair O(6)-methylguanine, and O(6)-methylguanine that escapes repair is recognized by the mismatch repair complex (see 120436), which activates apoptotic signals. STPG1 is required for O(6)-methylguanine-induced apoptosis (Fujikane et al., 2012).
▼ Cloning and Expression
Fujikane et al. (2012) cloned mouse Stpg1, which they called Mapo2. The deduced 341-amino acid protein is proline-rich and has 7 conserved PxPxxY repeats evenly distributed throughout the molecule. Database analysis revealed orthologs of Mapo2 in a wide variety of multicellular organisms. The deduced 334-amino acid human protein has a calculated molecular mass of 36.8 kD. Epitope-tagged mouse Mapo2 was expressed in both the cytoplasm and nucleus of transfected mouse lung fibroblasts.
▼ Gene Function
HeLa MR cells are unable to repair O(6)-methylguanine due to deficiency in MGMT expression. Fujikane et al. (2012) found that microRNA-mediated knockdown of MAPO2 in HeLa MR cells had no effect on cell proliferation. In addition, both HeLa MR cells and MAPO2-knockdown HeLa MR cells showed similar cell cycle checkpoint activation and accumulation of cells at G2/M phase following exposure to the alkylating agent N-methyl-N-nitrosourea (MNU). However, MAPO2-knockdown HeLa MR cells, but not parental HeLa MR cells, exhibited reduced induction of apoptosis in response to MNU, including inhibited formation of activated BAK (BAK1; 600516) dimers, reduced mitochondrial depolarization, and inefficient activation of CASP3 (600636). Fujikane et al. (2012) concluded that MAPO2 is required to induce apoptosis in response to O(6)-methylguanine.
By genomic sequence analysis, Fujikane et al. (2012) mapped the STPG1 gene to chromosome 1p36.11. They mapped the mouse Stpg1 gene to chromosome 4D3.