Separase loss of function cooperates with the loss of p53 in the initiation and progression of T- and B-cell lymphoma, leukemia and aneuploidy in mice

在小鼠中,T 细胞和 B 细胞淋巴瘤、白血病和非整倍体的发生和发展中,单独的酶功能丧失与 p53 的丧失协同作用

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作者:Malini Mukherjee, Gouqing Ge, Nenggang Zhang, Eryong Huang, Lanelle V Nakamura, Marissa Minor, Viacheslav Fofanov, Pullivarthi H Rao, Alan Herron, Debananda Pati

Background

Cohesin protease Separase plays a key role in faithful segregation of sister chromatids by cleaving the cohesin complex at the metaphase to anaphase transition. Homozygous deletion of ESPL1 gene that encodes Separase protein

Significance

Our results indicate that reduced levels of Separase act synergistically with loss of p53 in the initiation and progression of B- and T- cell lymphomas, which is aided by increased chromosomal missegregation and accumulation of genomic instability. ESPL1(+/hyp), p53(-/-) mice provide a new animal model for mechanistic study of aggressive lymphoma and also for preclinical evaluation of new agents for its therapy.

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