Abstract:
:The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Yu H,Suleiman H,Kim AH,Miner JH,Dani A,Shaw AS,Akilesh Sdoi
10.1128/MCB.00730-13subject
Has Abstractpub_date
2013-12-01 00:00:00pages
4755-64issue
23eissn
0270-7306issn
1098-5549pii
MCB.00730-13journal_volume
33pub_type
杂志文章abstract::In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.2.999
更新日期:1994-02-01 00:00:00
abstract::Etoposide, a nonintercalating antitumor drug, is a potent inhibitor of topoisomerase II activity. When Trypanosoma equiperdum is treated with etoposide, cleavable complexes are stabilized between topoisomerase II and kinetoplast DNA minicircles, a component of trypanosome mitochondrial DNA (T. A. Shapiro, V. A. Klein,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3660
更新日期:1994-06-01 00:00:00
abstract::In the "canonical" view of transforming growth factor beta (TGF-beta) signaling, Smad7 plays an inhibitory role. While Smad7 represses Smad3 activation by TGF-beta, it does not reverse the inhibitory effect of TGF-beta on myogenesis, suggesting a different function in myogenic cells. We previously reported a promyogen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01005-09
更新日期:2010-02-01 00:00:00
abstract::Autophagy is considered an adaptive mechanism against hyperosmotic stress. Although the process has been reported to be triggered by the inhibition of mTORC1, the precise downstream mechanisms remain elusive. Here, we demonstrate that hyperosmotic-stress-induced autophagy is different from conventional macroautophagy ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00024-19
更新日期:2019-07-29 00:00:00
abstract::To interrogate genes essential for cell growth, proliferation and survival in human cells, we carried out a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 screen in a B-cell lymphoma line using a custom extended-knockout (EKO) library of 278,754 single-guide RNAs (sgRNAs) that targe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00302-17
更新日期:2017-12-13 00:00:00
abstract::A mutant has been isolated from the J558 (immunoglobulin A, lambda, anti-alpha 1 leads to 3 dextran) cell line which synthesizes a heavy-chain immunoglobulin twice the size of normal heavy chain. Secondary variants that synthesized heavy chains either 1.5 times as large as wild type or the same size as wild type were ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.9.1134
更新日期:1982-09-01 00:00:00
abstract::The death domain-containing receptor superfamily and their respective downstream mediators control whether or not cells initiate apoptosis or activate NF-kappaB, events critical for proper immune system function. A screen for upstream activators of NF-kappaB identified a novel serine-threonine kinase capable of activa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6500
更新日期:1999-10-01 00:00:00
abstract::Inorganic pyrophosphate promoted the acidification of an intracellular compartment in permeabilized procyclic trypomastigotes of Trypanosoma brucei, as measured by acridine orange uptake. The proton gradient generated by pyrophosphate was collapsed by addition of nigericin or NH(4)Cl. Pyrophosphate-driven proton trans...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.11.7712
更新日期:1999-11-01 00:00:00
abstract::Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate a wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR is involved in the normal development and homeostasis of many organs. Here, we demo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00337-09
更新日期:2009-12-01 00:00:00
abstract::Poly(A) signals located at the 3' end of eukaryotic genes drive cleavage and polyadenylation at the same end of pre-mRNA. Although these sequences are expected only at the 3' end of genes, we found that strong poly(A) signals are also predicted within the 5' untranslated regions (UTRs) of many Drosophila melanogaster ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00919-10
更新日期:2011-02-01 00:00:00
abstract::Transfection experiments with constructs containing various 5'-deleted fragments of the human lipoprotein lipase (LPL) promoter and the chloramphenicol acetyltransferase reporter gene revealed an LPL silencer element (LSE) in the region of nucleotides -225 to -81 of the LPL gene that functioned in Chinese hamster ovar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.1.517
更新日期:1995-01-01 00:00:00
abstract::The J domain of simian virus 40 (SV40) large T antigen is required for efficient DNA replication and transformation. Despite previous reports demonstrating the promiscuity of J domains in heterologous systems, results presented here show the requirement for specific J-domain sequences in SV40 large-T-antigen-mediated ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.15.5749-5757.2000
更新日期:2000-08-01 00:00:00
abstract::Gonadotropin-releasing hormone (GnRH) interacts with a G protein-coupled receptor and increases the transcription of the glycoprotein hormone alpha-subunit gene. We have explored the possibility that mitogen-activated protein kinase (MAPK) plays a role in mediating GnRH effects on transcription. Activation of the MAPK...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.7.3531
更新日期:1995-07-01 00:00:00
abstract::The Saccharomyces cerevisiae mutant ref2-1 (REF = RNA end formation) was originally identified by a genetic strategy predicted to detect decreases in the use of a CYC1 poly(A) site interposed within the intron of an ACT1-HIS4 fusion reporter gene. Direct RNA analysis now proves this effect and also demonstrates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1689
更新日期:1995-03-01 00:00:00
abstract::Phospholipase Cgamma2 (PLCgamma2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLCgamma2-deficient mice had reduced immunoglobulin lambda (Iglambda) light-chain usage throughout B-cell maturation stages, including transitional type 1 (T1), transitional type 2 (T2), a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02273-06
更新日期:2007-09-01 00:00:00
abstract::Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00554-14
更新日期:2014-11-15 00:00:00
abstract::RBM25 has been shown to associate with splicing cofactors SRm160/300 and assembled splicing complexes, but little is known about its splicing regulation. Here, we characterize the functional role of RBM25 in alternative pre-mRNA splicing. Increased RBM25 expression correlated with increased apoptosis and specifically ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00560-08
更新日期:2008-10-01 00:00:00
abstract::Sequencing studies have shown that in somatic cells alternating runs of purines and pyrimidines are frequently associated with recombination crossover points. To test whether such sequences actually promote recombination, we have examined the effects of poly[d(pGpT).d(pApC)] and poly[d(pCpG).d(pCpG)] repeats on a homo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.11.3948
更新日期:1986-11-01 00:00:00
abstract::Lipophilic compounds such as retinoic acid and long-chain fatty acids regulate gene transcription by activating nuclear receptors such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptors (PPARs). These compounds also bind in cells to members of the family of intracellular lipid binding pr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.14.5114-5127.2002
更新日期:2002-07-01 00:00:00
abstract::Binding sites for six distinct nuclear factors on the 75-base-pair repeat of the Moloney murine leukemia virus enhancer have been identified by an electrophoretic mobility shift assay combined with methylation interference. Three of these factors, found in WEHI 231 nuclear extracts, which we have named LVa, LVb, and L...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.3.1101
更新日期:1987-03-01 00:00:00
abstract::Interleukin 4 (IL-4), an immunoregulatory cytokine, is produced only by a subset of activated T cells and cells of the mast cell-basophil lineage. The production of IL-4 by mast cells likely represents a significant source of this protein in local immune-inflammatory responses in the skin, brain, gastrointestinal, and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.228
更新日期:1996-01-01 00:00:00
abstract::Progression through mitosis requires the inactivation of the protein kinase activity of the p34cdc2-cyclin complex by a mechanism involving the degradation of cyclin. We have examined the stability in Xenopus egg extracts of radiolabeled Xenopus or sea urchin B-type cyclins synthesized in reticulocyte lysates. Xenopus...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1480
更新日期:1993-03-01 00:00:00
abstract::Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a lo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01271-08
更新日期:2009-03-01 00:00:00
abstract::E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here, we report that the HECT-type E3 ligase AIP...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00407-09
更新日期:2009-10-01 00:00:00
abstract::TIN2 is a negative regulator of telomere elongation that interacts with telomeric DNA repeat binding factor 1 (TRF1) and affects telomere length by a telomerase-dependent mechanism. Here we show that inactivation of the mouse TRF1-interacting protein 2 (TIN2) gene results in early embryonic lethality. We further obser...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.15.6631-6634.2004
更新日期:2004-08-01 00:00:00
abstract::The class II transactivator (CIITA) is induced by gamma interferon (IFN-gamma) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen alpha(2)(I) promoter via binding to CREB-binding prote...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.7078-7088.2001
更新日期:2001-10-01 00:00:00
abstract::Human 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) negatively regulate transcription elongation by RNA polymerase II (RNAPII) in vitro. However, the physiological roles of this negative regulation are not well understood. Here, by using a num...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02366-05
更新日期:2006-08-01 00:00:00
abstract::The polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14(ARF). Here we report that Bmi-1 is downregulated when WI-38 human fibroblasts undergo replicative senescence, but not quiescence, and extends replicative life span when overexpressed. Life span extension by Bmi-1 requ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.1.389-401.2003
更新日期:2003-01-01 00:00:00
abstract::Saccharomyces cerevisiae mating type switching is a gene conversion event that exhibits donor preference. MATa cells choose HMLalpha for recombination, and MATalpha cells choose HMRa. Donor preference is controlled by the recombination enhancer (RE), located between HMLalpha and MATa on the left arm of chromosome III....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.18.7976-7987.2005
更新日期:2005-09-01 00:00:00
abstract::Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02253-05
更新日期:2006-06-01 00:00:00