Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species. Numerous functions have been elucidated for Geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. Geminin is absent during G1 phase and accumulates through S, G2 phase and M phases of the cell cycle. Geminin levels drop at the metaphase / anaphase transition of mitosis when it is degraded by the Anaphase Promoting Complex (APC/C). During S phase, geminin is a positive regulator of DNA replication. In many cancer cell lines, inhibition of geminin by RNAi results in re-replication of portions of the genome, which leads to aneuploidy. In these cell lines, geminin knockdown leads to markedly slowed growth and apoptosis within several days. Recently, geminin has been found to be overexpressed in several malignancies and cancer cell lines.
Background References
1. "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity." Yanagi K., Mizuno T., You Z., Hanaoka F. J. Biol. Chem. 277:40871-40880(2002)
2. "Structural basis for inhibition of the replication licensing factor Cdt1 by geminin." Lee C., Hong B., Choi J.M., Kim Y., Watanabe S., Ishimi Y., Enomoto T., Tada S., Kim Y., Cho Y. Nature 430:913-917(2004)
Sequence Similarity
Belongs to the geminin family.
Post-translational Modification
Phosphorylated during mitosis. Phosphorylation at Ser-181 by CK2 results in enhanced binding to Hox proteins and more potent inhibitory effect on Hox transcriptional activity.
ICC staining Geminin in F9 cells (green). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS and counterstained with DAPI in order to highlight the nucleus (blue).
ICC staining Geminin in D3 cells (green). Cells were fixed in paraformaldehyde, permeabilised with 0.25% Triton X100/PBS and counterstained with DAPI in order to highlight the nucleus (blue).
Immunohistochemical analysis of paraffin-embedded human testis tissue with Rabbit anti-Geminin antibody (R1311-8) at 1/200 dilution.
The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) (high pressure) for 2 minutes. The tissues were blocked in 1% BSA for 20 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (R1311-8) at 1/200 dilution for 1 hour at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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