p150Glued, Dynein, and Microtubules Are Specifically Required for Activation of MKK3/6 and p38 MAPKs

Cheung, Po Yan; Zhang, Yi; Long, Jiafu; Lin, Sheng-Cai; Zhang, Mingjie; Jiang, Yong; Wu, Zhenguo

doi:10.1074/jbc.c400333200

Cited by 35 publications

(30 citation statements)

References 20 publications

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“…A potential unifying model is that NF-B may undergo active transport using dynein following stimulation, while shuttling may be diffusion-mediated. If shuttling is diffusionmediated, enhancement of the process by dynactin disruption could be consistent with emerging roles for dynactin in nonmotile processes such as tethering of signaling molecules (15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 56%

“…Dynactin can regulate the processivity of multiple molecular motors and dynactin disruption can disable both anterograde and retrograde trafficking (11,12); in addition, dynactin may act as a scaffold to dock anchoring or signaling proteins independently of its role in cellular transport (15)(16)(17)(18)(19). To directly assess the role of cytoplasmic dynein in the NF-B response to diverse activating stimuli in multiple cell types, we designed shRNAs against the heavy chain of dynein for both mouse and human species.…”

Section: Loss Of Endogenous Dynein Function Inhibits Stimulus-inducedmentioning

confidence: 99%

“…Kinesin has multiple family members, most of which mediate anterograde, but some of which also mediate retrograde movement (13,14). Potential roles for dynactin in nonmotile processes have also been recognized (15)(16)(17)(18)(19). This study tested the role of dynactin and dynein on the rate and amplitude of NF-B nuclear translocation under conditions of shuttling and in multiple activation paradigms.…”

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confidence: 99%

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Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex

Shrum¹,

DeFrancisco

Meffert

2009

Proc. Natl. Acad. Sci. U.S.A.

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Translocation from the cytoplasm to the nucleus is required for the regulation of gene expression by transcription factors of the nuclear factor kappa B (NF-B) family. The p65:p50 NF-B heterodimer that predominates in many cell types can undergo stimulated movement, following degradation of the I B inhibitor, as well as shuttling in the absence of stimulation with I B bound. Disruption of the dynactin complex and knockdown of endogenous dynein were used to investigate the nuclear translocation requirements for stimulated and shuttling movement of NF-B. A differential dependence of these two modes of transport on the dynein molecular motor and dynactin was found. NF-B used active dynein-dependent transport following stimulation while translocation during shuttling was mediated by a dynein-independent pathway that could be potentiated by dynactin disruption, consistent with a process of facilitated diffusion. Nuclear translocation and activation of NF-B-dependent gene expression showed a dependence on endogenous dynein in a variety of cell types and in response to diverse activating stimuli, suggesting that dyneindependent transport of NF-B may be a conserved mechanism in the NF-B activation pathway and could represent a potential point of regulation.NF-kappaB ͉ nuclear transport ͉ transcription ͉ molecular motor ͉ active transport T he NF-B or Rel transcription factors are ubiquitouslyexpressed regulators of gene expression that are essential for physiological processes ranging from innate and adaptive immunity to learning and memory. NF-B functions as a dimer and is retained in a latent form in the cytoplasm, bound to the inhibitor of NF-B (I B). In the canonical pathway, incoming stimuli trigger activation of the I B-kinase complex (IKK) that phosphorylates I B␣ and leads to its degradation. The subsequent translocation of active I B-free NF-B from cytoplasm to nucleus is critical for NF-B-dependent gene expression. In the absence of I B degradation, NF-B can undergo stimulusindependent movement back and forth between the nucleus and cytoplasm in a process termed shuttling (1). Shuttling of p65:p50 NF-B dimers is believed to result from incomplete masking of the p50 nuclear localization sequence (NLS) by bound I B␣ and can be observed by blocking exportin1/crm1-mediated nuclear export under unstimulated conditions (2).While NF-B requires importin family members to cross the nuclear pore (3), the molecular mechanisms underlying NF-B cytoplasmic movement remain poorly understood. Studies examining the role of microtubules are conflicting, possibly because the pharmacological agents that disrupt microtubules result in a confounding activation of NF-B (4-10). Microtubule-dependent transport can also be probed by disrupting the multisubunit dynactin complex, and it was recently reported that dynactin could play a role in the nuclear accumulation of neuronal NF-B (10). Dynactin regulates the processivity of molecular motors using microtubules, including cytoplasmic dynein and kinesin (11,12). Dynein is a retrograde m...

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Section: Discussionmentioning

confidence: 56%

Section: Loss Of Endogenous Dynein Function Inhibits Stimulus-inducedmentioning

confidence: 99%

mentioning

confidence: 99%

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Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex

Shrum¹,

DeFrancisco

Meffert

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Dyneins are microtubuleassociated motor protein complexes and has been reported that in vivo it is necessary for the activation of MAPK (mitogen-activated protein kinase) kinase3/6 and p38 (Cheung et al, 2004). The p38-MAPK pathway plays important roles in the regulation of several biological progresses including cell survival, differentiation, migration (Cuenda et al, 2007;Cuadrado et al, 2010), immune and inflammatory responses (Han et al, 1994;Lee et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants at 6p21.1 and 7p15.3 Identified by GWASs of Multiple Cancers and Ovarian Cancer Risk: a Case-control Study in Han Chinese Women

Li¹,

Han²,

Liu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers.

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“…B78H1 cells were maintained in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS). The construction and packaging of the equine macrophage cDNA library into the pFB murine retrovirus (7,48) were described earlier, and this library was kindly provided by Ron Montelaro (University of Pittsburgh). The EHV-1 lacZ reporter virus, L11⌬gI⌬gE was described previously (16).…”

Section: Methodsmentioning

confidence: 99%

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

Kurtz

Singletary

Kelly

et al. 2010

J Virol

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In this study, Equus caballus major histocompatibility complex class I (MHC-I) was identified as a cellular entry receptor for the alphaherpesvirus equine herpesvirus type 1 (EHV-1). This novel EHV-1 receptor was discovered using a cDNA library from equine macrophages. cDNAs from this EHV-1-susceptible cell type were inserted into EHV-1-resistant B78H1 murine melanoma cells, these cells were infected with an EHV-1 lacZ reporter virus, and cells that supported virus infection were identified by X-Gal (5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside) staining. Positive cells were subjected to several rounds of purification to obtain homogeneous cell populations that were shown to be uniformly infected with EHV-1. cDNAs from these cell populations were amplified by PCR and then sequenced. The sequence data revealed that the EHV-1-susceptible cells had acquired an E. caballus MHC-I cDNA. Cell surface expression of this receptor was verified by confocal immunofluorescence microscopy. The MHC-I cDNA was cloned into a mammalian expression vector, and stable B78H1 cell lines were generated that express this receptor. These cell lines were susceptible to EHV-1 infection while the parental B78H1 cells remained resistant to infection. In addition, EHV-1 infection of the B78H1 MHC-I-expressing cell lines was inhibited in a dose-dependent manner by an anti-MHC-I antibody.

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p150Glued, Dynein, and Microtubules Are Specifically Required for Activation of MKK3/6 and p38 MAPKs

Cited by 35 publications

References 20 publications

Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex

Stimulated nuclear translocation of NF-κB and shuttling differentially depend on dynein and the dynactin complex

Genetic Variants at 6p21.1 and 7p15.3 Identified by GWASs of Multiple Cancers and Ovarian Cancer Risk: a Case-control Study in Han Chinese Women

Equus caballus Major Histocompatibility Complex Class I Is an Entry Receptor for Equine Herpesvirus Type 1

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