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Matrix metalloproteinases (MMPs) are essential for proper extracellular matrix remodeling. We previously found that a membrane-anchored glycoprotein, RECK, negatively regulates MMP-9 and inhibits tumor invasion and metastasis. Here we show that RECK regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression, that mice lacking a functional RECK gene die around E10.5 with...
KChIP2, a gene encoding three auxiliary subunits of Kv4.2 and Kv4.3, is preferentially expressed in the adult heart, and its expression is downregulated in cardiac hypertrophy. Mice deficient for KChIP2 exhibit normal cardiac structure and function but display a prolonged elevation in the ST segment on the electrocardiogram. The KChIP2 -/- mice are highly susceptible to the induction...
To identify functions of the IKKα subunit of IκB kinase that require catalytic activity, we generated an Ikkα AA knockin allele containing alanines instead of serines in the activation loop. Ikkα AA/AA mice are healthy and fertile, but females display a severe lactation defect due to impaired proliferation of mammary epithelial cells. IKKα activity is required...
Mechanistic understanding of mammalian mRNA turnover remains incomplete. We demonstrate that the 3' to 5' exoribonuclease decay pathway is a major contributor to mRNA decay both in cells and in cell extract. An exoribonuclease-dependent scavenger decapping activity was identified that follows decay of the mRNA and hydrolyzes the residual cap. The decapping activity is associated with a subset of the...
We demonstrate through cell ablation, molecular genetic, and pharmacological approaches that during C. elegans male mating behavior, the male inserts his copulatory spicules into the hermaphrodite by regulating periodic and prolonged spicule muscle contractions. Distinct cholinergic neurons use different ACh receptors and calcium channels in the spicule muscles to mediate these contractile behaviors...
Proper spatial and temporal localization of specific mRNAs is pivotal in the early stages of development. To dissect the mechanisms of localization, several groups are employing advanced fluorescence microscopy to track RNA movements in live oocytes and embryos.
The plant hormone abscisic acid (ABA) regulates the aperture of the stomatal pore. The recent identification of new intermediates involved in ABA signaling suggests that this complex pathway is organized as a module-based network.
Several new papers report progress on the structure and function of Arp2/3 complex. A crystal structure, a cryo-EM structure, and a reconstitution of the complex from subunits have been reported. New results also address the nucleation mechanism and the role of bound nucleotide.
Coating of the X chromosome by Xist RNA is an essential trigger for X inactivation. However, little is known about the early chromatin remodeling events that transform this signal into transcriptional silencing. Here we report that methylation of histone H3 lysine 9 on the inactive X chromosome occurs immediately after Xist RNA coating and before transcriptional inactivation of X-linked genes. X-chromosomal...
Separation of sister chromatids in anaphase is mediated by separase, an endopeptidase that cleaves the chromosomal cohesin SCC1. Separase is inhibited by securin, which is degraded at the metaphase-anaphase transition. Using Xenopus egg extracts, we demonstrate that high CDC2 activity inhibits anaphase but not securin degradation. We show that separase is kept inactive under these conditions by a...
In Saccharomyces cerevisiae, mothers and daughters have distinct fates. We show that Cbk1 kinase and its interacting protein Mob2 regulate this asymmetry by inducing daughter-specific genetic programs. Daughter-specific expression is due to Cbk1/Mob2-dependent activation and localization of the Ace2 transcription factor to the daughter nucleus. Ectopic localization of active Ace2 to mother nuclei...
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