'We recently found that the metabolic sensor AMP-activated kinase (AMPK) inhibits the epithelial Na(+) channel (ENaC) through decreased plasma membrane ENaC expression, an effect requiring the presence of a binding motif in the cytoplasmic tail of the beta-ENaC subunit for the ubiquitin ligase Nedd4-2. To further examine the role of ... More
A dynamic switch between inhibitory and excitatory currents in a neuronal glutamate transporter.
AuthorsMelzer N, Torres-Salazar D, Fahlke C,
JournalProc Natl Acad Sci U S A
PubMed ID16365297
'Excitatory amino acid transporters (EAATs) terminate glutamatergic synaptic transmission and maintain extracellular glutamate concentrations in the central nervous system below excitotoxic levels. In addition to sustaining a secondary-active glutamate transport, EAAT glutamate transporters also function as anion-selective channels. Here, we report a gating process that makes anion channels associated with ... More
Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation of X chromosome-linked inhibitor of apoptosis (XIAP) and neither cause apoptosis.
AuthorsSilke J, Kratina T, Ekert PG, Pakusch M, Vaux DL,
JournalJ Biol Chem
PubMed ID14570909
'Grim is a Drosophila inhibitor of apoptosis (IAP) antagonist that directly interferes with inhibition of caspases by IAPs. Expression of Grim, or removal of DIAP1, is sufficient to activate apoptosis in fly cells. Transient expression of Grim in mammalian cells induces apoptosis, arguing for the conservation of apoptotic pathways, but ... More
Trpm7 regulates cell adhesion by controlling the calcium dependent protease calpain.
AuthorsSu LT, Agapito MA, Li M, T N Simonson W, Huttenlocher A, Habas R, Yue L, Runnels LW,
JournalJ Biol Chem
PubMed ID16436382
'M-calpain is a protease implicated in the control of cell adhesion through focal adhesion disassembly. The mechanism by which the enzyme is spatially and temporally controlled is not well understood, particularly because calpain''s dependence on calcium exceeds the sub-micromolar concentrations normally observed in cells. Here we show that the channel-kinase ... More
Hsp27 Enhances Recovery of Splicing as well as Rephosphorylation of SRp38 after Heat Shock.
Monitoring Editor: Greg Matera A heat stress causes a rapid inhibition of splicing. Exogenous expression of Hsp27 did not prevent that inhibition but enhanced the recovery of splicing afterward. Another small heat shock protein, alphaB-crystallin, had no effect. Hsp27, but not alphaB-crystallin, also hastened rephosphorylation of SRp38 - dephosphorylated a ... More
Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway.
AuthorsYoshizuka N, Yoshizuka-Chadani Y, Krishnan V, Zeichner SL,
JournalJ Virol
PubMed ID16103188
The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene expression. Some of Vpr's ... More
AuthorsXia ZB, Popovic R, Chen J, Theisler C, Stuart T, Santillan DA, Erfurth F, Diaz MO, Zeleznik-Le NJ,
JournalProc Natl Acad Sci U S A
PubMed ID16169901
MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions. Characterizing important downstream target genes of MLL and of MLL fusion proteins may provide rational therapeutic strategies for the treatment of MLL-associated leukemia. ... More
O-linked glycosylation at threonine 27 protects the copper transporter hCTR1 from proteolytic cleavage in mammalian cells.
AuthorsMaryon EB, Molloy SA, Kaplan JH,
JournalJ Biol Chem
PubMed ID17525160
The major human copper uptake protein, hCTR1, has 190 amino acids and a predicted mass of 21 kDa. hCTR1 antibodies recognize multiple bands in SDS-PAGE centered at 35 kDa. Part of this increased mass is due to N-linked glycosylation at Asn-15. We show that in mammalian cells the N15Q mutant ... More
Inducible XIST-dependent X-chromosome inactivation in human somatic cells is reversible.
AuthorsChow JC, Hall LL, Baldry SE, Thorogood NP, Lawrence JB, Brown CJ,
JournalProc Natl Acad Sci U S A
PubMed ID17537922
During embryogenesis, the XIST RNA is expressed from and localizes to one X chromosome in females and induces chromosome-wide silencing. Although many changes to inactive X heterochromatin are known, the functional relationships between different modifications are not well understood, and studies of the initiation of X-inactivation have been largely confined ... More
Toward a functional annotation of the human genome using artificial transcription factors.
AuthorsLee DK, Park JW, Kim YJ, Kim J, Lee Y, Kim J, Kim JS,
JournalGenome Res
PubMed ID14656973
We have developed a novel, high-throughput approach to collecting randomly perturbed gene-expression profiles from the human genome.A human 293 cell library that stably expresses randomly chosen zinc-finger transcription factors was constructed, and the expression profile of each cell line was obtained using cDNA microarray technology.Gene expression profiles from a total ... More
Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes.
Cell number is an important determinant of adipose tissue mass, and the coordinated proliferation and differentiation of preadipocytes into mature lipid-laden adipocytes underpins the increased adipose tissue mass associated with obesity. Despite this, the molecular cues governing such adipose tissue expansion are poorly understood. We previously reported that fibroblast growth ... More