Net1 (also called ArhGEF8) is a RhoA-specific GEF (guanine nucleotide exchange factors). Net1 binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor kB activation []. In nucleus, it also regulates RhoB-mediated cell death after DNA damage []. Net1 and RhoA have been shown to play important roles in various aspects of vertebrate embryonic development and organogenesis [].Net1 contains a catalytic Dbl homology (DH) domain and an adjacent pleckstrin homology (PH) domain flanked by N- and C-terminal extensions []. This entry represents the PH domain. The DH and PH domains are necessary for binding to the GTPase and stimulating nucleotide exchange activity [].
This entry represents a group of fungal nucleolar proteins, including Dnt1 from fission yeasts and Tof2/Net1 from budding yeasts. Net1 regulates the homologous MEN (mitotic exit network) pathway by sequestering Cdc14 phosphatase in the nucleolus before mitotic exit []. Dnt1 is a homologue of Net1. Both Dnt1 and Net1 negatively regulate the homologous SIN (septation initiation network) and MEN pathways. They are both required for rDNA silencing and minichromosome maintenance. However, Net1 regulates the MEN through the Cdc14 phosphatase, while Dnt1 inhibit SIN signaling independently of Clp1 (a Cdc14-family phosphatase) [].Tof2 is a paralogue of Net1. It is required for rDNA silencing and mitotic rDNA condensation [, ]. It coordinates the biphasic release of Cdc14 during anaphase by restraining a population of Cdc14 in the nucleolus [].
