title: Interplay between the transcription factor Zif and aPKC regulates neuroblast polarity and self-renewal.
abstract: How a cell decides to self-renew or differentiate is a critical issue in stem cell and cancer biology. Atypical protein kinase C (aPKC) promotes self-renewal of Drosophila larval brain neural stem cells, neuroblasts. However, it is unclear how aPKC 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 aPKC. aPKC 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 aPKC transcription. We further show that Zif is phosphorylated by aPKC both in vitro and in vivo. Phosphorylation of Zif by aPKC excludes it from the nucleus, leading to Zif inactivation in neuroblasts. Thus, reciprocal repression between Zif and aPKC act as a critical regulatory mechanism for establishing cell polarity and controlling neuroblast self-renewal.
authors.affiliation: Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604.
authors.forename: Kai Chen
authors.initials: KC
authors.lastname: Chang
authors.forename: Gisela
authors.initials: G
authors.lastname: Garcia-Alvarez
authors.forename: Gregory
authors.initials: G
authors.lastname: Somers
authors.forename: Rita
authors.initials: R
authors.lastname: Sousa-Nunes
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Rossi
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Lee
authors.forename: Swee Beng
authors.initials: SB
authors.lastname: Soon
authors.forename: Cayetano
authors.initials: C
authors.lastname: Gonzalez
authors.forename: William
authors.initials: W
authors.lastname: Chia
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors; C554335:Zif protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C