Disease relevance of MCM3AP

• RESULTS: We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb) to MCM3AP (46.6 Mb), with part of them expressed aberrantly in the Down's syndrome mouse model [1].
• Map80 was expressed in Escherichia coli as a fusion with His6 tag and purified with sequential column chromatographies [2].
• OBJECTIVES: To investigate whether GANP and phosphorylated-GANP (P-GANP) are expressed in cultured human melanocytes and melanoma cells and in benign and malignant melanocytic lesions [3].
• Hypotension (MAP 80 per cent of control or less) occurred in 24, mothers (54 per cent), often transiently, but an infused fluid volume exceeding 30 ml X kg-1 at delivery significantly reduced post-delivery hypotension [4].

High impact information on MCM3AP

• GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is induced by CD40-mediated signaling in vitro and in the germinal center B cells stimulated with antigen in vivo [5].
• Overexpression of ganp cDNA in Daudi B cells caused the increased DNA synthesis more than the levels of the mock-transfectants [5].
• Germinal center-associated nuclear protein (GANP) has a phosphorylation-dependent DNA-primase activity that is up-regulated in germinal center regions [5].
• The recombinant GANP fragment covering this region synthesizes RNA primers for extension by DNA polymerase I with single-stranded DNA templates in vitro [5].
• Hence, MCM3AP is a potent natural inhibitor of the initiation of DNA replication whose action is mediated by interaction with MCM3 [6].

Biological context of MCM3AP

• We show here that wild type MCM3AP, but not the acetylase-deficient mutant, inhibits initiation of DNA replication, but not elongation [6].
• In the present study, we examined inhibition of the cell cycle by MCM3AP in a cell-free system [6].
• Furthermore, the chromatin binding of MCM3AP is temporally correlated with that of endogenous MCM3 when cells were released from mitosis [6].
• The carboxyl-terminal 721-amino-acid sequence of hGANP is identical to Map80, that is presumably generated by alternative splicing of hganp/Map80 gene [7].
• These evidences suggested that the novel DNA-primase GANP is involved in regulation of cell proliferation of antigen-driven B cells in germinal centers [5].

Anatomical context of MCM3AP

• The hGANP, with the domain (Map-box) capable of binding to MCM3 in B cells, might be involved in regulation of cell-cycle progression and DNA replication of GC-B cells [7].
• Increased expression of germinal center-associated nuclear protein (GANP) is associated with malignant transformation of melanocytes [3].
• Since this up-regulation has not been detected in T cells in GCs and in Concanavalin A-stimulated T cells in vitro, selective function of GANP molecule on B cell proliferation and differentiation might exist [8].

Associations of MCM3AP with chemical compounds

• This study also indicates that MCM3AP contains putative acetyl CoA binding motifs conserved within the GCN5-related N-acetyltransferase superfamily [9].

Physical interactions of MCM3AP

• GANP and MCM3AP can bind to the MCM3 protein involved in initiation of DNA replication [10].

Regulatory relationships of MCM3AP

• The addition of recombinant Map80 stimulated the amount of nuclear localized MCM3 [2].

Other interactions of MCM3AP

• Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication [7].
• Functional interaction between the glucocorticoid receptor and GANP/MCM3AP [10].
• Involvement of GANP in B cell activation in T cell-dependent antigen response [8].

Analytical, diagnostic and therapeutic context of MCM3AP

• 3. Northern blot analysis with RNAs from various organs demonstrated a single band of 7kb hganp mRNA, which suggests a preferential transcription of hganp gene from the hganp/Map80 locus [7].
• Glutathione-S-transferase-pull-down and co-immunoprecipitation assays showed that the C-terminal domain of GANP, encompassing MCM3AP, interacts with the ligand-binding domain of the glucocorticoid receptor [10].
• GANP and P-GANP expression in melanocytic lesions was analyzed by immunohistochemistry [3].

References