Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage

Article

关键词: NEUROBLAST SELF-RENEWAL;    RIBOSOMAL-RNA SYNTHESIS;    ASYMMETRIC DIVISION;    TUMOR-SUPPRESSOR;    PROLIFERATION;    MELANOGASTER;    PROTEIN;    CANCER;    POLARITY;    BRAIN;   

DOI  :  10.1038/nature07014

来源: SCIE

【 摘 要 】

Drosophila neuroblasts(1) and ovarian stem cells(2,3) are well characterized models for stem cell biology. In both cell types, one daughter cell self- renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim - NHL( tripartite motif and Ncl- 1, HT2A and Lin- 41 domain)- containing protein Brain tumour ( Brat) into one of the two daughter cells(4-6), ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit- amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim - NHL protein Mei- P26 ( refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei- P26 expression is low in stem cells but is strongly induced in 16- cell cysts. In mei- P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei- P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute- 1, a component of the RISC complex, as a common binding partner of Brat and Mei- P26, and show that Mei- P26 acts by inhibiting the microRNA pathway. Mei- P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.

【 授权许可】

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