WTX: an unexpected regulator for p53

The WTX gene is frequently lost or mutated in Wilms tumor. In this issue of Molecular Cell, Kim et al. (2012) identify WTX modulation of p53 tumor-suppressor activity through regulation of p53 acetylation. Therefore, WTX differentially regulates the oncogenic β-catenin pathway and the tumor-suppressing p53 pathway.     

MipZ: one for the pole, two for the DNA

In this issue of Molecular Cell,Kiekebusch et al. (2012) show that a novel regulatory mechanism of the ATPase cycle of MipZ, together with nonspecific DNA binding, generates the MipZ gradient that spatially regulates Z ring formation in Caulobacter crescentus.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).     

A cell-specific enhancer of the mouse alpha 1-antitrypsin gene has multiple functional regions and corresponding protein-binding sites.

We have previously described the isolation and characterization of genomic clones corresponding to the mouse alpha 1-antitrypsin gene (Krauter et al., DNA 5:29-36, 1986). In this report, we have analyzed the DNA sequences upstream of the RNA start site that direct hepatoma cell-specific expression of this gene when incorporated into recombinant plasmids. The 160 nucleotides 5' to the cap site direct low-level expression in hepatoma cells, and sequences between -520 and -160 bp upstream of the RNA start site functioned as a cell-specific enhancer of expression both with the alpha 1-antitrypsin promoter and when combined with a functional beta-globin promoter. Within the enhancer region, three binding sites for proteins present in hepatoma nuclear extracts were identified. The location of each site was positioned, using both methylation protection and methylation interference experiments. Each protein-binding site correlated with a functionally important region necessary for full enhancer activity. These experiments demonstrated a complex arrangement of regulatory elements comprising the alpha 1-antitrypsin enhancer. Significant qualitative differences exist between the findings presented here and the cis-acting elements operative in regulating expression of the human alpha 1-antitrypsin gene (Ciliberto et al., Cell 41:531-540, 1985; De Simone et al., EMBO J. 6:2759-2766, 1987).     

Regulation of macromolecular traffic mediated by the nuclear pore complex.

A sophisticated selective mechanism that regulates nuclear-cytoplasmic traffic has evolved in eukaryotes which circumvents the formidable barrier presented by the nuclear envelope. The sites of RNA and protein exchanges are the nuclear pore complexes (NPCs), 125 MDa supramolecular assemblies inserted into the envelope (see recent reviews by Dingwall, 1991; Goldfarb and Michaud, 1991; Miller et al., 1991; Nigg et al., 1991). In this article, the role NPCs play in regulating intracellular macromolecular traffic will be discussed.     

Axon trapping: constructing the visual system one layer at a time

Zhang et?al. (2012) and Rozas et?al. (2012) in this issue of Neuron find that cysteine string protein α, a protein involved in neurodegeneration, regulates vesicle endocytosis via interaction with dynamin 1, which may participate in regulating synaptic transmission and possibly in maintaining synapses.     

Genome-Wide Analysis of Gene Expression in Stationary Phase and Genetic Characterization of Stationary-Phase-Dependent Halocin Gene Expression in the Haloarchaeon Haloferax mediterranei

The stationary phase of microbial growth is a very complex state regulated by various environmental and physiological factors.An intensive study of stationary phase could promote a comprehensive understanding of the complete life cycle of microorganisms,and may provide important insights into their adaptation to harsh and nutrient-depleted conditions.Although the underlying mechanisms have been well-studied in bacteria and yeasts (Herman,2002;Navarro Llorens et al.,2010),less is known about this growth phase in archaea yet.The haloarchaeon Haloferax mediterranei has served as a good model for studying haloarchaeal physiology and metabolism for several decades because of its accelerated growth,remarkable metabolic ability and genomic stability (Han et al.,2012).During stationary phase,H.mediterranei can produce halocin H4 (Cheung et al.,1997),synthesize gas vesicles (J(a)ger et al.,2002),secrete extracellular polysaccharide (Antón et al.,1988) and accumulate poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)(Cai et al.,2012).Due to these specific features,we selected H.mediterranei as a model system to investigate the archaeal gene expression and regulation during the stationary phase.     

Calcium and repression in malaria sex: knowing when the time is right

Plasmodium falciparum PfEMP1 is a malaria virulence protein whose expression is epigenetically regulated. The parasite's ability to express exclusively only one of the sixty var genes that encode PfEMP1 is essential for disease pathogenesis. Two recent papers identify key molecular players in determining whether a var gene is active or silenced (Volz et?al., 2012; Zhang et?al., 2011).     

Bone cells crosstalk: noncanonical Roring in the Wnt

It is well established that canonical Wnt signaling in bone regulates bone mass. Much less is known about the?role of noncanonical Wnt signaling. Maeda and colleagues now report in Nature Medicine that Wnt5a-Ror2 crosstalk between bone cells enhances bone resorption, thereby negatively regulating skeletal homeostasis (Maeda et?al., 2012).     

Immune plexins and semaphorins: old proteins,new immune functions

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.     

Mice mutant for Ppap2c, a homolog of the germ cell migration regulator wunen, are viable and fertile

Phosphatidic acid phosphatases (PAPs) catalyze the conversion of phosphatidic acid to diacylglycerol and inorganic phosphate and have been postulated to function both in lipid biosynthesis and in cellular signal transduction. In Drosophila melanogaster, the Type 2 phosphatidic acid phosphatase protein encoded by the wunen gene, negatively regulates primordial germ cell migration. We recently described the cloning and characterization of the mouse Ppap2c gene, which encodes the Type 2 phosphatidic acid phosphatase Pap2c (Zhang et al., Genomics 63:142-144). To analyze the in vivo role of the Ppap2c gene we constructed a null mutation by gene targeting. Ppap2c(-/-) homozygous mutant mice were viable, fertile, and exhibited no obvious phenotypic defects. These data demonstrate that the Ppap2c gene is not essential for embryonic development or fertility in mice.     

The 5'-flanking sequence and regulatory elements of the cystatin S gene.

The gene encoding rat cystatin S (Cys S), a salivary gland-specific secretory protein, has CAAT and TATA boxes upstream of the inititation codon (Cox and Shaw, 1992), and contains regions that resemble those of other hormonally responsive eukaryotic genes. The 5'-flanking sequence of the rat Cys S gene has a potential CREB/AP-1 binding site (Rupp et al., 1990; Trejo et al., 1992), two potential glucocorticoid responsive elements (GREs, Drouin et al., 1989), and a possible GR/PR (glucocorticoid/progesterone) responsive element (Forman and Samuels, 1990). One of these potential GREs is adjacent to a potential AP-2 binding site, and another is typical of the glucocorticoid and progesterone receptor binding site. In this report, we have identified three regions in the 5'-flanking region of the Cys S gene that are found in salivary gland-specific genes (Ting et al., 1992) with a GT-rich region located between conserved elements II and III. Transfection experiments described in this paper suggest that a 281-bp DNA fragment from the Cys S gene promoter region with conserved elements II and III, the GT-rich region, and a possible GR/PR responsive element contains a negative regulatory element. In addition, our experiments suggest that the GT-rich region by itself is acting as a positive regulatory element.     

A glimpse at the evolution of virulence control

Studies of the accessory gene regulator (agr) of Staphylococcus aureus often focus on the associated RNA regulator RNAIII. Recently, Queck et al. (2008) reported on RNAIII-independent gene regulation in highly virulent, community-associated S. aureus and proposed that two independent regulatory systems were integrated during the pathogenic evolution of S. aureus.