High impact information on Gmnn

• All cells in geminin-deficient embryos commit to the trophoblast cell lineage and consist of trophoblast giant cells (TGCs) only [1].
• Geminin is also down-regulated in TGCs of wild-type blastocysts during S and gap-like phases by proteasome-mediated degradation, suggesting that loss of geminin is part of the mechanism regulating endoreduplication [1].
• Most factors including cyclins, Cdc6, and geminin are rather constitutively expressed during the cell cycle of ES cells [2].
• Here we show that geminin is regulated transcriptionally by the retinoblastoma tumor suppressor (RB)/E2F pathway [3].
• Geminin is targeted for repression by the retinoblastoma tumor suppressor pathway through intragenic E2F sites [3].

Biological context of Gmnn

• The geminin protein is a critical regulator of DNA replication [3].
• Our results suggest that geminin is essential for cooperative progression of the cell cycle through S phase to M phase during the preimplantation stage of mouse development [4].
• DNA fragmentation in neuronal nuclei was detected at 3 h, and atypical expression of cell cycle- and stress-regulated proteins such as geminin, cdk2, cdk4, and cytochrome c became apparent at 2 to 48 h [5].

Anatomical context of Gmnn

• Similarly, an acute loss of Rb in mouse adult fibroblasts deregulated geminin RNA and protein levels [3].

Physical interactions of Gmnn

• Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin [6].

Other interactions of Gmnn

• Initially, we observed that the activation of RB led to the repression of geminin transcription [3].
• Structural basis for inhibition of the replication licensing factor Cdt1 by geminin [6].
• This licensing control is achieved through the activities of geminin and cyclin-dependent kinases [6].

References