Expression of RAB27B is up-regulated in senescent human cells

Fujii, Michihiko; Kawai, Yoshinori; Endoh, Morio; Hossain, Mohammad Nazir; Nakabayashi, Kazuhiko; Ayusawa, Dai

doi:10.1016/j.mad.2006.03.001

Cited by 21 publications

(15 citation statements)

References 18 publications

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“…High expression of Rab25, one of Rab GTPases, is found in ovarian and breast cancer (Cheng et al, 2004). Another subtype of Rab GTPase, Rab27B, is enhanced in senescent human fibroblast (Fujii et al, 2006). It is unclear whether increases of theses Rab GTPases are causes or consequences of aging.…”

Section: Resultsmentioning

confidence: 99%

Misexpression screen delineates novel genes controlling Drosophila lifespan

Paik

Jang²,

Lee³

et al. 2012

Mechanisms of Ageing and Development

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In an initial preliminary screen we identified factors associated with controlling Drosophila aging by examining longevity in adults where EP elements induced over-expression or antisense-RNA at genes adjacent to each insertion. Here, we study 45 EP lines that initially showed at least 10% longer mean lifespan than controls. These 45 lines and a daughterless (da)-Gal4 stock were isogenized into a CS10 wild-type background. Sixteen EP lines corresponding to 15 genes significantly extended lifespan when their target genes were driven by da-Gal4. In each case, the target genes were seen to be over-expressed. Independently derived UAS-gene transgenic stocks were available or made for two candidates: ImpL2 which is ecdysone-inducible gene L2, and CG33138, 1,4-alpha-glucan branching enzyme. With both, adult lifespan was increased upon over-expression via the GeneSwitch inducible Gal4 driver system. Several genes in this set of 15 correspond to previously discovered longevity assurance systems such as insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new potential mechanisms for the control of aging including mRNA synthesis and maturation, intracellular vesicle trafficking, and neuroendocrine regulation.

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Section: Resultsmentioning

confidence: 99%

Misexpression screen delineates novel genes controlling Drosophila lifespan

Paik

Jang²,

Lee³

et al. 2012

Mechanisms of Ageing and Development

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“…It has also been reported that cellular senescence of cervical cancer cells induces expression of several Rab genes including Rab5B, which plays important roles in endosome maturation (Wells et al., ). Another report showed that expression of Rab27B, which promotes the secretion of EVs, is enhanced in senescent fibroblasts (Fujii et al., ). It is known that EV secretion contributes to the clearance of harmful molecules in the cells (Desdín‐Micó & Mittelbrunn, ), such as cytoplasmic DNA.…”

Section: Cellular Senescence Increases Ev Secretionmentioning

confidence: 99%

Emerging roles of extracellular vesicles in cellular senescence and aging

2018

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SummaryCellular senescence is a cellular program that prevents the proliferation of cells at risk of neoplastic transformation. On the other hand, age‐related accumulation of senescent cells promotes aging at least partially due to the senescence‐associated secretory phenotype, whereby cells secrete high levels of inflammatory cytokines, chemokines, and matrix metalloproteinases. Emerging evidence, however, indicates that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment. Senescent cells secrete more EphA2 and DNA via EVs, which can promote cancer cell proliferation and inflammation, respectively. Extracellular vesicles secreted from DNA‐damaged cells can also affect telomere regulation. Furthermore, it has now become clear that EVs actually play important roles in many aspects of aging. This review is intended to summarize these recent progresses, with emphasis on relationships between cellular senescence and EVs.

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“…Furthermore, disruption of axonal retrograde transport of neurotrophin might contribute to age-related diseases such as Alzheimer’s disease and Down syndrome, suggesting the involvement of Rab proteins [ 234 ]. In fact, the expression profile of cells committed to senescence has been studied in various systems and alterations in Rab protein expression have been detected [ 235 , 236 , 237 ]. For instance, Rab3a expression decreases during aging and in Alzheimer’s disease [ 237 ].…”

Section: Neurodegenerative and Age-related Diseases: Consequences mentioning

confidence: 99%

The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

2014

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Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC) and p75NTR, a member of the tumor necrosis factor (TNF) receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways.

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Expression of RAB27B is up-regulated in senescent human cells

Cited by 21 publications

References 18 publications

Misexpression screen delineates novel genes controlling Drosophila lifespan

Misexpression screen delineates novel genes controlling Drosophila lifespan

Emerging roles of extracellular vesicles in cellular senescence and aging

The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

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