Pttg1/securin is required for the branching morphogenesis of the mammary gland and suppresses mammary tumorigenesis.

Pituitary tumor transforming gene 1 (Pttg1) encodes the mammalian securin, which is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis). PTTG1 is overexpressed in a number of human cancers and has been suggested to be an oncogene. However, we found that, in Pttg1-mutant females, the mammary epithelial cells showed increased proliferation and precocious branching morphogenesis.

Inhibitory phosphorylation of separase is essential for genome stability and viability of murine embryonic germ cells.

Activity of separase, a cysteine protease that cleaves sister chromatid cohesin at the onset of anaphase, is tightly regulated to ensure faithful chromosome segregation and genome stability. Two mechanisms negatively regulate separase: inhibition by securin and phosphorylation on serine 1121. To gauge the physiological significance of the inhibitory phosphorylation, we created a mouse strain in which Ser1121 was mutated to Ala (S1121A).

Securin and separase phosphorylation act redundantly to maintain sister chromatid cohesion in mammalian cells.

The spindle assembly checkpoint monitors the integrity of the spindle microtubules, which attach to sister chromatids at kinetochores and play a vital role in preserving genome stability by preventing missegregation. A key target of the spindle assembly checkpoint is securin, the separase inhibitor. In budding yeast, loss of securin results in precocious sister chromatid separation when the microtubule spindle is disrupted.

DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint.

Mitotic catastrophe is the response of mammalian cells to mitotic DNA damage. It produces tetraploid cells with a range of different nuclear morphologies from binucleated to multimicronucleated. In response to DNA damage, checkpoints are activated to delay cell cycle progression and to coordinate repair.

Dynamic gene expression during the onset of myoblast differentiation in vitro.

Skeletal myogenesis is a well-studied differentiation process. However, despite the identification and functional characterization of the myogenic basic HLH transcription factors, molecular details are still lacking. With the advent of microarray technology, it has become possible to look at changes in gene expression profiles in a biological process on an unprecedented scale.