The Ime2 protein kinase enhances the disassociation of the Sum1 repressor from middle meiotic promoters.

Meiotic development in Saccharomyces cerevisiae (sporulation) is controlled by the sequential transcription of temporally distinct sets of meiosis-specific genes. The induction of middle genes controls exit from meiotic prophase, the completion of the nuclear divisions, and spore formation. Middle promoters are controlled through DNA elements termed middle sporulation elements (MSEs) that are bound by the Sum1 repressor during vegetative growth and by the Ndt80 activator during meiosis.

The chaperone activity of GRP94 toward insulin-like growth factor II is necessary for the stress response to serum deprivation.

Insulin-like growth factor (IGF)-II is a hormone with mitogenic activity for many cell types and tissues. We demonstrate that its intracellular processing and secretion strictly depend on the endoplasmic reticulum chaperone glucose-regulated protein (GRP) 94. GRP94 interacts physically and transiently with pro-IGF-II intermediates, and its activity is essential for secretion of active IGF-II, thus establishing IGF-II as a client of GRP94.

Deficient SUMO attachment to Flp recombinase leads to homologous recombination-dependent hyperamplification of the yeast 2 microm circle plasmid.

Many Saccharomyces cerevisiae mutants defective in the SUMO pathway accumulate elevated levels of the native 2 microm circle plasmid (2 microm). Here we show that accumulation of 2 microm in the SUMO pathway mutants siz1Delta siz2Delta, slx5Delta, and slx8Delta is associated with formation of an aberrant high-molecular-weight (HMW) form of 2 microm. Characterization of this species from siz1Delta siz2Delta showed that it contains tandem copies of the 2 mum sequence as well as single-stranded DNA.

The Ras/cAMP pathway and the CDK-like kinase Ime2 regulate the MAPK Smk1 and spore morphogenesis in Saccharomyces cerevisiae.

Meiotic development (sporulation) in the yeast Saccharomyces cerevisiae is induced by nutritional deprivation. Smk1 is a meiosis-specific MAP kinase homolog that controls spore morphogenesis after the meiotic divisions have taken place. In this study, recessive mutants that suppress the sporulation defect of a smk1-2 temperature-sensitive hypomorph were isolated.

GRP94 is essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion.

Because only few of its client proteins are known, the physiological roles of the endoplasmic reticulum chaperone glucose-regulated protein 94 (GRP94) are poorly understood. Using targeted disruption of the murine GRP94 gene, we show that it has essential functions in embryonic development. grp94-/- embryos die on day 7 of gestation, fail to develop mesoderm, primitive streak, or proamniotic cavity.

Increased islet apoptosis in Pdx1+/- mice.

Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. Glucose sensing and islet Ca(2+) responses were also normal.