14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport

Brunet, Anne; Kanai, Fumihiko; Stehn, Justine R.; Xu, Jian; Sarbassova, Dilara; Frangioni, John V.; Dalal, Sorab N.; DeCaprio, James A.; Greenberg, Michael E.; Yaffe, Michael B.

doi:10.1083/jcb.200112059

Cited by 502 publications

(457 citation statements)

References 38 publications

(94 reference statements)

Supporting

Mentioning

422

Contrasting

Unclassified

Order By: Relevance

“…FKHRL1 is a transcription factor 23,28,36,37 and to be active its nuclear abundance is mandatory. Also phosphorylation at serine 253 defines cytoplasmic localisation by disrupting a nuclear localisation signal (NLS) on FKHRL1.…”

Section: Cdc25a and Apoptosismentioning

confidence: 99%

See 1 more Smart Citation

Subcellular localisation of Cdc25A determines cell fate

et al. 2003

View full text Add to dashboard Cite

Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKBprotein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.

show abstract

Section: Cdc25a and Apoptosismentioning

confidence: 99%

“…Also phosphorylation at serine 253 defines cytoplasmic localisation by disrupting a nuclear localisation signal (NLS) on FKHRL1. 36 Both phosphorylation sites may cooperate in determining the subcellular distribution of FKHRL1. The regulatory functions of phosphorylated serine 315 and of other phosphosites are currently unknown.…”

Section: Cdc25a and Apoptosismentioning

confidence: 99%

Subcellular localisation of Cdc25A determines cell fate

et al. 2003

View full text Add to dashboard Cite

show abstract

“…14-3-3 binding may decrease the ability of FoxOs to bind DNA, releasing FoxOs from DNA [17]. 14-3-3 binding to FoxOs may promote the nuclear export of FoxOs by inducing a conformational change in FoxO molecules that would expose the NES and allow interaction with Exportin/Crm1 [16]. 14-3-3 binding to FoxOs may also prevent the nuclear import of FoxOs by masking FoxO nuclear localization signal (NLS) [18,19] (Fig.…”

Section: Regulation Of Phosphorylation and Subcellular Localizationmentioning

confidence: 99%

The FoxO transcription factors and metabolic regulation

2007

View full text Add to dashboard Cite

Forkhead transcription factors FoxOs are conserved beyond species and regulated by insulin signaling pathway. FoxOs have diverse functions on differentiation, proliferation and cell survival. In calorie restriction (CR) or starvation, FoxOs are in nucleus, active transcriptionally, and increase hepatic glucose production, decrease insulin secretion, increase food intake and cause degradation of skeletal muscle for supplying substrates for glucose production. However, even in insulin resistance due to excessive calorie intake, FoxOs are active and causes type 2 diabetes and hyperlipidemia. The understanding of molecular mechanism how FoxOs affect glucose or lipid metabolism will shed light on the novel therapy of type 2 diabetes and the metabolic syndrome.

show abstract

“…14-3-3 proteins are phosphoserine/threonine binding proteins that play important roles in many regulatory processes, including intracellular protein targeting. 22,23 To explore whether zyxin interacts with 14-3-3 proteins, we conducted a co-immunoprecipitation assay. Wild-type zyxin and S142D mutant robustly bound to both g and z isoforms of 14-3-3, whereas S142A mutant failed to bind g isoform, but it still tightly associated with z isoform (Figure 5a).…”

Section: Resultsmentioning

confidence: 99%

Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation

Liu

Tang

et al. 2007

Cell Death Differ

View full text Add to dashboard Cite

Zyxin, a focal adhesion molecule, contains LIM domains and shuttles between the cytoplasm and the nucleus. Nuclear zyxin promotes cardiomyocyte survival, which is mediated by nuclear-activated Akt. However, the molecular mechanism of how zyxin antagonizes apoptosis remains elusive. Here, we report that zyxin binds to acinus-S, a nuclear speckle protein inducing apoptotic chromatin condensation after cleavage by caspases, and prevents its apoptotic action, which is regulated by Akt. Akt binds and phosphorylates zyxin on serine 142, leading to its association with acinus. Interestingly, 14-3-3c, but not f isoform selectively, triggers zyxin nuclear translocation, which is Akt phosphorylation dependent. Zyxin is also a substrate of caspases, but Akt phosphorylation is unable to prevent its apoptotic cleavage. Expression of zyxin S142D, a phosphorylation mimetic mutant, diminishes acinus proteolytic cleavage and chromatin condensation; by contrast, wild-type zyxin or unphosphorylated S142A mutant fails. Thus, Akt regulates zyxin/acinus complex formation in the nucleus, contributing to suppression of apoptosis. Cell Death and Differentiation (2007) Zyxin is a phosphoprotein that accumulates with integrins at cell-substratum attachment sites. It has a proline-rich domain (PRD) at the N-terminus and multiple LIM domains in Cterminal half. The PRD region displays docking sequences for several proteins in actin assembly and organization, and SH3 domains that are found in a number of proteins in signal transduction pathways. [1][2][3][4][5][6][7] The LIM domain is a double-zincfinger motif that presents in proteins involved in the regulation of cell proliferation and differentiation. 8,9 Zyxin shuttles between the nucleus and sites of cell adhesion in fibroblasts, and is thus an excellent candidate for relaying information between these two compartments. 10 Although some of zyxin family proteins, including Trip6 and Ajuba, affect nuclear transcription, 11 no definite evidence has yet demonstrated that zyxin is implicated in this process.Acinus, predominantly located in the nucleus, induces apoptotic chromatin condensation after cleavage by caspases. 12 It is cleaved at both its N-and C-termini, generating a p17 active form (amino acids (aa) 228-335), which triggers chromatin condensation. Acinus contains a region similar to the RNA recognition motif of Drosophila splicing regulator Sxl, suggesting that it is implicated in RNA metabolism. Indeed, acinus is a component of functional splicesomes. 13 Acinus is also found in the apoptosis-and splicing-associated protein (ASAP) complex, which is comprised of SAP18, RNPS1, and distinct isoforms of acinus. Addition of the complex to in vitro splicing assays inhibits RNA processing. 14 Moreover, knockdown of acinus inhibits oligonucleosomal DNA fragmentation during apoptosis. 15 Acinus is also a component of exon junction complex (EJC), which is deposited on exon-intron junctions during pre-mRNA splicing, and stimulates gene expression at the RNA level. 16 Recently, we show that ...

show abstract

14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport

Cited by 502 publications

References 38 publications

Subcellular localisation of Cdc25A determines cell fate

Subcellular localisation of Cdc25A determines cell fate

The FoxO transcription factors and metabolic regulation

Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation

Contact Info

Product

Resources

About