Interplay between the transcription factor Zif and aPKC regulates neuroblast polarity and self-renewal.

How a cell decides to self-renew or differentiate is a critical issue in stem cell and cancer biology. Atypical protein kinase C promotes self-renewal of Drosophila larval brain neural stem cells, neuroblasts. However, it is unclear how cortical polarity and protein levels are regulated. Here, we have identified a zinc-finger protein, Zif, which is required for the expression and asymmetric localization of aduanyu1531 displays ectopic cortical localization with upregulated protein levels in dividing zif mutant neuroblasts, leading to neuroblast overproliferation. We show that Zif is a transcription factor that directly represses aduanyu1531 transcription. We further show that Zif is phosphorylated by aduanyu1531 both in vitro and in vivo. Phosphorylation of Zif by aduanyu1531 excludes it from the nucleus, leading to Zif inactivation in neuroblasts. Thus, reciprocal repression between Zif and aduanyu1531 act as a critical regulatory mechanism for establishing cell polarity and controlling neuroblast self-renewal.

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