Karyopherin Msn5 is involved in a novel mechanism controlling the cellular level of cell cycle regulators Cln2 and Swi5
ABSTRACT The yeast β-karyopherin Msn5 controls the SBF cell-cycle transcription factor, responsible for the periodic expression of CLN2 cyclin gene at G1/S, and the nuclear export of Cln2 protein. Here we show that Msn5 regulates Cln2 by an additional mechanism. Inactivation of Msn5 causes a severe reduction in the cellular content of Cln2. This occurs by a post-transcriptional mechanism, since CLN2 mRNA level is not importantly affected in asynchronous cultures. Cln2 stability is not significantly altered in msn5 cells and inactivation of Msn5 causes a reduction in protein level even when Cln2 is stabilized. Therefore, the reduced amount of Cln2 in msn5 cells is mainly due not to a higher …
Production and characterisation of recombinant forms of human pulmonary surfactant protein C (SP-C):Structure and surface activity
Udgivelsesdato: 2006-Apr Surfactant protein C (SP-C) is an essential component for the surface tension-lowering activity of the pulmonary surfactant system. It contains a valine-rich alpha helix that spans the lipid bilayer, and is one of the most hydrophobic proteins known so far. SP-C is also an essential component of various surfactant preparations of animal origin currently used to treat neonatal respiratory distress syndrome (NRDS) in preterm infants. The limited supply of this material and the risk of transmission of infectious agents and immunological reactions have prompted the development of synthetic SP-C-derived peptides or recombinant humanized SP-C for inclusion in new prepar…
Regulation of cell cycle transcription factor Swi5 by karyopherin Msn5
AbstractInactivation of S. cerevisiae β-karyopherin Msn5 causes hypersensitivity to the overexpression of mitotic cyclin Clb2 and aggravates growth defects of many mutant strains in mitotic exit, suggesting a connection between Msn5 and mitotic exit. We determined that Msn5 controlled subcellular localization of the mitotic exit transcription factor Swi5, since it was required for Swi5 nuclear export. Msn5 physically interacted with the N-terminal end of Swi5. Inactivation of Msn5 caused a severe reduction in cellular levels of Swi5 protein. This effect occurred by a post-transcriptional mechanism, since SWI5 mRNA levels were not affected. The reduced amount of Swi5 in msn5 mutant cells was…
Yeast karyopherin Kap95 is required for cell cycle progression at Start
Abstract Background The control of the subcellular localization of cell cycle regulators has emerged as a crucial mechanism in cell division regulation. The active transport of proteins between the nucleus and the cytoplasm is mediated by the transport receptors of the β-karyopherin family. In this work we characterized the terminal phenotype of a mutant strain in β-karyopherin Kap95, a component of the classical nuclear import pathway. Results When KAP95 was inactivated, most cells arrested at the G2/M phase of the cell cycle, which is in agreement with the results observed in mutants in the other components of this pathway. However, a number of cells accumulate at G1, suggesting a novel r…
Spatial regulation of the Start repressor Whi5
The Saccharomyces cerevisiae Start repressor Whi5, the functional analogue of mammalian pRB, shuttles between the nucleus and the cytoplasm throughout the cell cycle: enters into the nucleus at the end of mitosis and remains nuclear until Start. We studied the mechanisms involved in this spatial regulation. The nuclear import depends on the beta-karyopherins of the classical import pathway Kap95 and Cse1. Whi5 contains a monopartite and a bipartite classical NLS localized in its N-terminal region which are functionally redundant. A fragment of Whi5 containing these NLSs is able to constitutively accumulate a GFP(4) protein inside the nucleus throughout the cell cycle, which suggests that th…