Abstract:
:The Forkhead family of transcription factors participates in the induction of death-related genes. In NMuMG and 4T1 mammary epithelial cells, transforming growth factor beta (TGF beta) induced phosphorylation and cytoplasmic retention of the Forkhead factor FKHRL1, while reducing FHKRL1-dependent transcriptional activity. TGF beta-induced FKHRL1 phosphorylation and nuclear exclusion were inhibited by LY294002, an inhibitor of phosphatidylinositol-3 kinase. A triple mutant of FKHRL1, in which all three Akt phosphorylation sites have been mutated (TM-FKHRL1), did not translocate to the cytoplasm in response to TGF beta. In HaCaT keratinocytes, expression of dominant-negative Akt prevented TGF beta-induced 1) reduction of Forkhead-dependent transcription, 2) FKHRL1 phosphorylation, and 3) nuclear exclusion of FKRHL1. Forced expression of either wild-type (WT) or TM-FKHRL1, but not a FKHRL1 mutant with deletion of the transactivation domain, resulted in NMuMG mammary cell apoptosis. Evidence of nuclear fragmentation colocalized to cells with expression of WT- or TM-FKHRL1. The apoptotic effect of WT-FKHRL1 but not TM-FKHRL1 was prevented by exogenous TGF beta. Serum starvation-induced apoptosis was also inhibited by TGF beta in NMuMG and HaCaT cells. Finally, dominant-negative Akt abrogated the antiapoptotic effect of TGF beta. Taken together, these data suggest that TGF beta may play a role in epithelial cell survival via Akt-dependent regulation of FKHRL1.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Shin I,Bakin AV,Rodeck U,Brunet A,Arteaga CLdoi
10.1091/mbc.12.11.3328keywords:
subject
Has Abstractpub_date
2001-11-01 00:00:00pages
3328-39issue
11eissn
1059-1524issn
1939-4586journal_volume
12pub_type
杂志文章abstract::We previously characterized major components of mitotic chromosomes assembled in Xenopus laevis egg extracts and collectively referred to them as Xenopus chromosome-associated polypeptides (XCAPs). They included five subunits of the condensin complex essential for chromosome condensation. In an effort to identify nove...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.01-09-0441
更新日期:2002-01-01 00:00:00
abstract::Hyaluronan (HA) in the endothelial glycocalyx serves as a mechanotransducer for high-shear-stress-stimulated endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production. Low shear stress (LSS) has been shown to contribute to endothelial inflammation and atherosclerosis by impairing the ba...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-04-0241
更新日期:2016-12-15 00:00:00
abstract::Gene expression in eukaryotes is an essential process that includes transcription, RNA processing, and export. One important player in this interface is the poly(A)(+)-RNA-binding protein Nab2, which regulates the mRNA poly(A)(+)-tail length and export. Here we show that Nab2 has additional roles during mRNA transcrip...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-01-0055
更新日期:2011-08-01 00:00:00
abstract::Cell morphogenesis depends on polarized exocytosis. One widely held model posits that long-range transport and exocyst-dependent tethering of exocytic vesicles at the plasma membrane sequentially drive this process. Here, we describe that disruption of either actin-based long-range transport and microtubules or the ex...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-08-0720
更新日期:2011-01-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that counteracts replicative telomere erosion by adding telomeric sequence repeats onto chromosome ends. Despite its well-established role in telomere synthesis, telomerase has not yet been detected at telomeres. The RNA component of human telomerase (hTR) resides in the nucleo...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-09-0904
更新日期:2006-02-01 00:00:00
abstract::The majority of Rab proteins are posttranslationally modified with two geranylgeranyl lipid moieties that enable their stable association with membranes. In this study, we present evidence to demonstrate that there is a specific lipid requirement for Rab protein localization and function. Substitution of different pre...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-11-0707
更新日期:2003-05-01 00:00:00
abstract::Drosophila myosin IB (Myo1B) is one of two class I myosins in the Drosophila genome. In the larval and adult midgut enterocyte, Myo1B is present within the microvillus (MV) of the apical brush border (BB) where it forms lateral tethers between the MV membrane and underlying actin filament core. Expression of green flu...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-02-0191
更新日期:2007-11-01 00:00:00
abstract::Surface charges at the inner leaflet of the plasma membrane may contribute to regulate the surface recruitment of key signaling factors. Phosphatidylserine (PS) is an abundant charged lipid that may regulate charge distribution in different cell types. Here we characterize the subcellular distribution and function of ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-06-0353
更新日期:2017-01-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaste...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-09-0745
更新日期:2012-03-01 00:00:00
abstract::We have previously identified a novel family of proteins called the GGAs (Golgi-localized, gamma-ear-containing, ADP-ribosylation factor-binding proteins). These proteins consist of an NH(2)-terminal VHS domain, followed by a GAT domain, a variable domain, and a gamma-adaptin ear homology domain. Studies from our own ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.11.3573
更新日期:2001-11-01 00:00:00
abstract::Human HT2-19 cells with a conditional cdk1 mutation stop dividing upon cdk1 inactivation and undergo multiple rounds of endoreplication. We show herein that major cell cycle events remain synchronized in these endoreplicating cells. DNA replication alternates with gap phases and cell cycle-specific cyclin E expression...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-12-0850
更新日期:2003-09-01 00:00:00
abstract::Tumor cells use actin-rich protrusions called invadopodia to degrade extracellular matrix (ECM) and invade tissues; related structures, termed podosomes, are sites of dynamic ECM interaction. We show here that supervillin (SV), a peripheral membrane protein that binds F-actin and myosin II, reorganizes the actin cytos...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-08-0867
更新日期:2009-02-01 00:00:00
abstract::Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence-bas...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-05-0305
更新日期:2017-09-15 00:00:00
abstract::Polyadenylation-induced translation is an important regulatory mechanism during metazoan development. During Xenopus oocyte meiotic progression, polyadenylation-induced translation is regulated by CPEB, which is activated by phosphorylation. XGef, a guanine exchange factor, is a CPEB-interacting protein involved in th...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-07-0585
更新日期:2005-03-01 00:00:00
abstract::The amino acid-derived polyamines are organic cations that are essential for growth in all mammalian cells, but their exact roles at the molecular level remain largely unknown. Here we provide evidence that polyamines promote the translation of cyclin-dependent kinase 4 (CDK4) by the action of CUG-binding protein 1 (C...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-01-0069
更新日期:2011-09-01 00:00:00
abstract::In Tetrahymena thermophila, peptides secreted via dense-core granules, called mucocysts, are generated by proprotein processing. We used expression profiling to identify candidate processing enzymes, which localized as cyan fluorescent protein fusions to mucocysts. Of note, the aspartyl cathepsin Cth3p plays a key rol...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-03-0833
更新日期:2014-08-15 00:00:00
abstract::An increase in the level of active, GTP-bound Ras is not necessary for transformation of chicken embryo fibroblasts (CEF) by v-Src. This suggests that other Ras-independent pathways contribute to transformation by v-Src. To address the possibility that activation of phosphatidylinositol-3-kinase (PI3K) and the mammali...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.10.6.1693
更新日期:1999-06-01 00:00:00
abstract::Cell-cell fusion is an intriguing differentiation process, essential for placental development and maturation. A proteomic approach identified a cytoplasmic protein, calponin 3 (CNN3), related to the fusion of BeWo choriocarcinoma cells. CNN3 was expressed in cytotrophoblasts in human placenta. CNN3 gene knockdown pro...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-03-0261
更新日期:2010-11-15 00:00:00
abstract::Isu, the scaffold protein on which Fe-S clusters are built in the mitochondrial matrix, plays a central role in the biogenesis of Fe-S cluster proteins. We report that the reduction in the activity of several components of the cluster biogenesis system, including the specialized Hsp70 Ssq1, causes a 15-20-fold up-regu...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-06-0622
更新日期:2008-12-01 00:00:00
abstract::Timely down-regulation of the evolutionarily conserved protein kinase Swe1 plays an important role in cell cycle control, as Swe1 can block nuclear division through inhibitory phosphorylation of the catalytic subunit of cyclin-dependent kinase. In particular, Swe1 degradation is important for budding yeast cell surviv...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-02-0127
更新日期:2011-07-01 00:00:00
abstract::During stem cell divisions, mitotic microtubules do more than just segregate the chromosomes. They also determine whether a cell divides virtually symmetrically or asymmetrically by establishing spindle orientation and the plane of cell division. This can be decisive for the fate of the stem cell progeny. Spindle defe...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E15-03-0152
更新日期:2015-12-01 00:00:00
abstract::Capture of newly synthesized proteins into endoplasmic reticulum (ER)-derived coat protomer type II (COPII) vesicles represents a critical juncture in the quality control of protein biogenesis within the secretory pathway. The yeast ATP-binding cassette transporter Yor1p is a pleiotropic drug pump that shows homology ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-01-0046
更新日期:2007-09-01 00:00:00
abstract::The small GTPase Ran is essential for spindle assembly. Ran is proposed to act through its nuclear import receptors importin alpha and/or importin beta to control the sequestration of proteins necessary for spindle assembly. To date, the molecular mechanisms by which the Ran pathway functions remain unclear. Using pur...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-07-0454
更新日期:2004-01-01 00:00:00
abstract::Autophagy is a central homeostasis and stress response pathway conserved in all eukaryotes. One hallmark of autophagy is the de novo formation of autophagosomes. These double-membrane vesicular structures form around and deliver cargo for degradation by the vacuole/lysosome. Where and how autophagosomes form are outst...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-07-0381
更新日期:2013-09-01 00:00:00
abstract::The efficient activation of p90(rsk) by MAP kinase requires their interaction through a docking site located at the C-terminal end of p90(rsk). The MAP kinase p42(mpk1) can associate with p90(rsk) in G(2)-arrested but not in mature Xenopus oocytes. In contrast, an N-terminally truncated p90(rsk) mutant named D2 consti...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.10.9.2971
更新日期:1999-09-01 00:00:00
abstract::The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells and hippocampal neurons in culture. TI-VAMP interacts with plasma membrane and e...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-03-0147
更新日期:2003-10-01 00:00:00
abstract::Condensins are highly conserved proteins that are important for chromosome maintenance in nearly all forms of life. Although many organisms employ two forms of the condensin complex, the condensin genes in Tetrahymena have expanded even further. Here we report a form of condensin that is specifically active during sex...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E18-08-0487
更新日期:2019-05-15 00:00:00
abstract::Cysteine string protein (Csp) is essential for neurotransmitter release in Drosophila. It has been suggested that Csp functions by regulating the activity of presynaptic Ca2+ channels, thus controlling exocytosis. We have examined the effect of overexpressing Csp1 in PC12 cells, a neuroendocrine cell line. PC12 cell c...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.9.8.2259
更新日期:1998-08-01 00:00:00
abstract::Yeast and vertebrate nuclear pores display significant morphological similarity by electron microscopy, but sequence similarity between the respective proteins has been more difficult to observe. Herein we have identified a vertebrate nucleoporin, Nup93, in both human and Xenopus that has proved to be an evolutionaril...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.8.10.2017
更新日期:1997-10-01 00:00:00
abstract::Microtubules (MTs) have been proposed to act mechanically as compressive struts that resist both actomyosin contractile forces and their own polymerization forces to mechanically stabilize cell shape. To identify the origin of MT bending, we directly observed MT bending and F-actin transport dynamics in the periphery ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-09-0909
更新日期:2009-06-01 00:00:00