Interplay between the Transcription Factor Zif and aPKC Regulates Neuroblast Polarity and Self-Renewal

TY - JOUR

T1 - Interplay between the Transcription Factor Zif and aPKC Regulates Neuroblast Polarity and Self-Renewal

AU - Chang, Kai Chen

AU - Garcia-Alvarez, Gisela

AU - Somers, Gregory

AU - Sousa-Nunes, Rita

AU - Rossi, Fabrizio

AU - Lee, Ying Ying

AU - Soon, Swee Beng

AU - Gonzalez, Cayetano

AU - Chia, William

AU - Wang, Hongyan

PY - 2010/11/16

Y1 - 2010/11/16

N2 - 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

AB - 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

U2 - 10.1016/j.devcel.2010.10.007

DO - 10.1016/j.devcel.2010.10.007

M3 - Article

SN - 1534-5807

VL - 19

SP - 778

EP - 785

JO - Developmental Cell

JF - Developmental Cell

IS - 5

M1 - N/A

ER -