Abstract:
:Welander distal myopathy (WDM) is a muscle dystrophy characterized by adult-onset distal muscle weakness, prevalently impacting the distal long extensors of the hands and feet. WDM is an autosomal dominant disorder caused by a missense mutation (c.1362G>A; p.E384K) in the TIA1 (T-cell intracellular antigen 1) gene, which encodes an RNA-binding protein basically required for the posttranscriptional regulation of RNAs. We have developed a heterologous cell model of WDM to study the molecular and cellular events associated with mutated TIA1 expression. Specifically, we analyzed how this mutation affects three regulatory functions mediated by TIA1: (i) control of alternative SMN2 (survival motor neuron 2) splicing; (ii) formation, assembly, and disassembly of stress granules; and (iii) mitochondrial dynamics and its consequences for mitophagy, autophagy, and apoptosis. Our results show that whereas WDM-associated TIA1 expression had only a mild effect on SMN2 splicing, it led to suboptimal adaptation to environmental stress, with exacerbated stress granule formation that was accompanied by mitochondrial dysfunction and autophagy. Overall, our observations indicate that some aspects of the cell phenotype seen in muscle of patients with WDM can be recapitulated by ectopic expression of WDM-TIA1 in embryonic kidney cells, highlighting the potential of this model to investigate the pathogenesis of this degenerative disease and possible therapeutics.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Carrascoso I,Sánchez-Jiménez C,Silion E,Alcalde J,Izquierdo JMdoi
10.1128/MCB.00299-18subject
Has Abstractpub_date
2018-12-11 00:00:00issue
1eissn
0270-7306issn
1098-5549pii
MCB.00299-18journal_volume
39pub_type
杂志文章abstract::The tetradecanoyl phorbol acetate-induced sequence 7 gene (tis7) is regulated during cell fate processes and functions as a transcriptional coregulator. Here, we describe the generation and analysis of mice lacking the tis7 gene. Surprisingly, TIS7 knockout mice show no gross histological abnormalities and are fertile...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.8.3514-3525.2004
更新日期:2004-04-01 00:00:00
abstract::Using a sensitive transfection-tumorigenicity assay, we have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5016
更新日期:1991-10-01 00:00:00
abstract::Tumor-promoting phorbol esters affect a variety of cellular functions which may underlie tumor promotion. We isolated from human lymphocytes a cDNA clone whose gene is inducible by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate as well as by the T-cell mitogen phytohemagglutinin. Nuclear transcription experim...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2540
更新日期:1984-11-01 00:00:00
abstract::Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative fun...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5041-5049.2001
更新日期:2001-08-01 00:00:00
abstract::Sequence data are presented for the Saccharomyces cerevisiae TAP1 gene and for a mutant allele, tap1-1, that activates transcription of the promoter-defective yeast SUP4 tRNA(Tyr) allele SUP4A53T61. The degree of in vivo activation of this allele by tap1-1 is strongly affected by the nature of the flanking DNA sequenc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3434
更新日期:1993-06-01 00:00:00
abstract::c-jun is a member of the family of immediate-early genes whose expression is induced by factors such as serum stimulation, phorbol ester, and differentiation signals. Here we show that increased Jun synthesis after serum stimulation is accompanied by a concomitant increase in phosphorylation. Several serine-threonine ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.10.4694
更新日期:1992-10-01 00:00:00
abstract::We report that newly synthesized mRNA poly(A) tails are matured to precise lengths by the Pab1p-dependent poly(A) nuclease (PAN) of Saccharomyces cerevisiae. These results provide evidence for an initial phase of mRNA deadenylation that is required for poly(A) tail length control. In RNA 3'-end processing extracts lac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.11.6548
更新日期:1998-11-01 00:00:00
abstract::The E1B 19-kilodalton protein (19K protein) is a potent apoptosis inhibitor and the adenovirus homolog of Bcl-2 (E. White, Genes Dev. 10:1-15, 1996). To obtain a better understanding of the biochemical mechanism by which the E1B 19K protein regulates apoptosis, proteins that interact with 19K have been identified; one...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.10.5857
更新日期:1996-10-01 00:00:00
abstract::We studied RNA polymerase I transcription in cells transfected with a plasmid, prHuTK, containing the herpes simplex virus tk gene fused to a human rRNA promoter. Primer extension analysis of tk RNA isolated from COS cells transfected with prHuTK reveals that transcription from the RNA polymerase I promoter is highly ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.2.352
更新日期:1985-02-01 00:00:00
abstract::Mutation in the REC2 gene of Ustilago maydis leads to defects in DNA repair, recombination, and meiosis. Analysis of the primary sequence of the Rec2 protein reveals a region with significant homology to bacterial RecA protein and to the yeast recombination proteins Dmc1, Rad51, and Rad57. This homologous region in th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6287
更新日期:1994-09-01 00:00:00
abstract::A new dominant amplifiable selective system for use in bacterium-animal cell shuttle vectors was developed by the insertion of a 2-kilobase genomic fragment containing the cloned Escherichia coli gene for asparagine synthetase (AS) into the pBR322-simian virus 40 recombinant vector pSV2 so as to place the translationa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1623
更新日期:1987-05-01 00:00:00
abstract::The Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, and hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00569-16
更新日期:2017-08-11 00:00:00
abstract::The imprinted expression of the H19 and Igf2 genes in the mouse is controlled by an imprinting control center (ICR) whose activity is regulated by parent-of-origin differences in methylation. The only protein that has been implicated in ICR function is the zinc-finger protein CTCF, which binds at multiple sites within...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.10.3855-3863.2005
更新日期:2005-05-01 00:00:00
abstract::Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease (HD). The downstream targets that mediate its inhibitory effects on huntingtin (Htt) aggregation and toxicity are unknown. We have identified profilin, a small actin-binding factor that also interacts with Htt, as bei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00079-08
更新日期:2008-09-01 00:00:00
abstract::Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01469-10
更新日期:2011-05-01 00:00:00
abstract::The ability of basic helix-loop-helix muscle regulatory factors (MRFs), such as MyoD, to convert nonmuscle cells to a myogenic lineage is regulated by numerous growth factor and oncoprotein signaling pathways. Previous studies have shown that H-Ras 12V inhibits differentiation to a skeletal muscle lineage by disruptin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.3547
更新日期:1997-07-01 00:00:00
abstract::Determining the functions of novel genes implicated in cell survival is directly relevant to our understanding of mammalian development and carcinogenesis. ARS2 is an evolutionarily conserved gene that confers arsenite resistance on arsenite-sensitive Chinese hamster ovary cells. Little is known regarding the function...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01565-07
更新日期:2008-03-01 00:00:00
abstract::The hexanucleotide AAUAAA has been demonstrated to be part of the signal for cleavage and polyadenylation at appropriate sites on eucaryotic mRNA precursors. Since this sequence is not unique to polyadenylation sites, it cannot be the entire signal for the cleavage event. We have extended the definition of the polyade...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.8.1460
更新日期:1984-08-01 00:00:00
abstract::Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse emb...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.10.3705-3714.2000
更新日期:2000-05-01 00:00:00
abstract::Yeast cells are keenly sensitive to the availability and quality of nutrients. Addition of glucose to cells growing on a poorer carbon source elicits a cell cycle delay during G1 phase and a concomitant increase in the cell size. The signal is transduced through the RAS-cyclic AMP pathway. Using synchronized populatio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.2492
更新日期:1998-05-01 00:00:00
abstract::Histone N-terminal tails are central to the processes that modulate nucleosome structure and function. We have studied the contribution of core histone tails to the structure of a single nucleosome and to a histone (H3-H4)(2) tetrameric particle assembled on a topologically constrained DNA minicircle. The effect of hi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.19.7230-7237.2000
更新日期:2000-10-01 00:00:00
abstract::NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.5929
更新日期:1991-12-01 00:00:00
abstract::Glucocorticoid production in the adrenal cortex is activated in response to an increase in cyclic AMP (cAMP) signaling. The nuclear protein p54(nrb)/NONO belongs to the Drosophila behavior/human splicing (DBHS) family and has been implicated in several nuclear processes, including transcription, splicing, and RNA expo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00993-14
更新日期:2015-04-01 00:00:00
abstract::We show that the nuclear genes for the cytoplasmic and mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa are distinct in their encoded proteins, codon usage, mRNA levels, and regulation. The 4.2-kilobase-pair region representing the structural gene for cytoplasmic LeuRS and flanking regions has been se...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.11.4645
更新日期:1989-11-01 00:00:00
abstract::An RNA editing mechanism modifies apolipoprotein B (apo-B) mRNA in the intestine by converting cytosine at nucleotide (nt) 6666 to uracil. To define the sequence requirements for editing, mutant apo-B RNAs were analyzed for the ability to be edited in vitro by enterocyte extracts. Editing was detected by a sensitive a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.12.7288
更新日期:1993-12-01 00:00:00
abstract::In Blastocladiella emersonii zoospores, a set of proteins was found associated with the ribosomes and free ribonucleoprotein particles distinct from the ribosomes and polyribosomes. These proteins were designated P120, P105, P64, P56, and P42 based on their molecular weights determined by gel electrophoresis. Synthesi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.1.4.310
更新日期:1981-04-01 00:00:00
abstract::The upstream promoter sequences of the human carbonic anhydrase II (CA II) gene have been studied by 5' deletion analysis. Promoter activity was assayed by transfection and chloramphenicol acetyltransferase assay in both human HeLa cells and murine L cells. This investigation showed that the CA II promoter is comparab...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4589
更新日期:1987-12-01 00:00:00
abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00552-06
更新日期:2006-08-01 00:00:00
abstract::We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00019-15
更新日期:2015-08-01 00:00:00
abstract::Myb family proteins are ubiquitously expressed transcription factors. In mammalian cells, they play a critical role in regulating the G(1)/S cell cycle transition but their role in regulating other cell cycle checkpoints is incompletely defined. Herein, we report experiments which demonstrate that c-Myb upregulates cy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01100-06
更新日期:2007-03-01 00:00:00