Protein Transport

Publication Title: 
International Journal of Hematology

FKHRL1 is one of the human homologues of DAF-16, which is concerned with longevity in Caenorhabditis elegans. Previously, we demonstrated that FKHRL1 functions downstream of Akt in erythropoietin (EPO) signaling and that it is directly phosphorylated by activated Akt. Because phosphorylated FKHRL1 loses its transcriptional activity and translocates into the cytoplasm, FKHRL1 appears to be nonfunctional in the presence of EPO.

Author(s): 
Uchida, Mie
Kirito, Keita
Endo, Hitoshi
Ozawa, Keiya
Komatsu, Norio
Publication Title: 
Molecular Biology of the Cell

Short, repetitive, G-rich telomeric sequences are synthesized by telomerase, a ribonucleoprotein consisting of telomerase reverse transcriptase (TERT) and an integrally associated RNA. Human TERT (hTERT) can repetitively reverse transcribe its RNA template, acting processively to add multiple telomeric repeats onto the same substrate. We investigated whether certain threshold levels of telomerase activity and processivity are required to maintain telomere function and immortalize human cells with limited lifespan.

Author(s): 
D'Souza, Yasmin
Chu, Tsz Wai
Autexier, Chantal
Publication Title: 
PloS One

Mutations in the fused in sarcoma/translated in liposarcoma gene (FUS/TLS, FUS) have been identified in sporadic and familial forms of amyotrophic lateral sclerosis (ALS). FUS is an RNA-binding protein that is normally localized in the nucleus, but is mislocalized to the cytoplasm in ALS, and comprises cytoplasmic inclusions in ALS-affected areas. However, it is still unknown whether the neurodegeneration that occurs in ALS is caused by the loss of FUS nuclear function, or by the gain of toxic function due to cytoplasmic FUS aggregation.

Author(s): 
Sasayama, Hiroshi
Shimamura, Mai
Tokuda, Takahiko
Azuma, Yumiko
Yoshida, Tomokatsu
Mizuno, Toshiki
Nakagawa, Masanori
Fujikake, Nobuhiro
Nagai, Yoshitaka
Yamaguchi, Masamitsu
Publication Title: 
Molecular Vision

PURPOSE: Human eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins.

Author(s): 
Stewart, Daniel N.
Lango, Jozsef
Nambiar, Krishnan P.
Falso, Miranda J. S.
FitzGerald, Paul G.
Rocke, David M.
Hammock, Bruce D.
Buchholz, Bruce A.
Publication Title: 
Biomaterials

Carbon nanotubes (CNTs) are one of widely used nanomaterials in industry and biomedicine. The potential impact of single-walled carbon nanotubes (SWCNTs) was evaluated using Caenorhabditis elegans (C. elegans) as a toxicological animal model. SWCNTs are extremely hydrophobic to form large agglomerates in aqueous solutions. Highly soluble amide-modified SWCNTs (a-SWCNTs) were therefore used in the present study so that the exact impact of SWCNTs could be studied. No significant toxicity was observed in C. elegans due to the amide modification.

Author(s): 
Chen, Po-Hsuan
Hsiao, Kuang-Ming
Chou, Cheng-Chung
Publication Title: 
Nature Communications

It is hypothesized that a common underlying mechanism links multiple neurodegenerative disorders. Here we show that transitional endoplasmic reticulum ATPase (TERA)/valosin-containing protein (VCP)/p97 directly binds to multiple polyglutamine disease proteins (huntingtin, ataxin-1, ataxin-7 and androgen receptor) via polyglutamine sequence. Although normal and mutant polyglutamine proteins interact with TERA/VCP/p97, only mutant proteins affect dynamism of TERA/VCP/p97.

Author(s): 
Fujita, Kyota
Nakamura, Yoko
Oka, Tsutomu
Ito, Hikaru
Tamura, Takuya
Tagawa, Kazuhiko
Sasabe, Toshikazu
Katsuta, Asuka
Motoki, Kazumi
Shiwaku, Hiroki
Sone, Masaki
Yoshida, Chisato
Katsuno, Masahisa
Eishi, Yoshinobu
Murata, Miho
Taylor, J. Paul
Wanker, Erich E.
Kono, Kazuteru
Tashiro, Satoshi
Sobue, Gen
La Spada, Albert R.
Okazawa, Hitoshi
Publication Title: 
The Journal of Cell Biology

We identified and characterized a human orthologue of Rif1 protein, which in budding yeast interacts in vivo with the major duplex telomeric DNA binding protein Rap1p and negatively regulates telomere length. Depletion of hRif1 by RNA interference in human cancer cells impaired cell growth but had no detectable effect on telomere length, although hRif1 overexpression in S. cerevisiae interfered with telomere length control, in a manner specifically dependent on the presence of yeast Rif1p.

Author(s): 
Xu, Lifeng
Blackburn, Elizabeth H.
Publication Title: 
Molecular and Cellular Biology

Telomerase canonically maintains telomeres, but recent reports have suggested that the core protein mammalian telomerase reverse transcriptase (TERT) component, together with the chromatin remodeling factor BRG1 and ?-catenin, may also bind to and promote expression of Wnt target genes. However, this proposed noncanonical role of TERT in Wnt signaling has been controversial. Here, we investigated the effects of human TERT (hTERT) on Wnt signaling in human breast cancer lines and HeLa cells.

Author(s): 
Listerman, Imke
Gazzaniga, Francesca S.
Blackburn, Elizabeth H.
Publication Title: 
EMBO molecular medicine

Loss of function of the FMR1 gene leads to fragile X syndrome (FXS), the most common form of intellectual disability. The loss of FMR1 function is usually caused by epigenetic silencing of the FMR1 promoter leading to expansion and subsequent methylation of a CGG repeat in the 5' untranslated region. Very few coding sequence variations have been experimentally characterized and shown to be causal to the disease. Here, we describe a novel FMR1 mutation and reveal an unexpected nuclear export function for the C-terminus of FMRP.

Author(s): 
Okray, Zeynep
de Esch, Celine E. F.
Van Esch, Hilde
Devriendt, Koen
Claeys, Annelies
Yan, Jiekun
Verbeeck, Jelle
Froyen, Guy
Willemsen, Rob
de Vrij, Femke M. S.
Hassan, Bassem A.
Publication Title: 
The International Journal of Neuropsychopharmacology

BACKGROUND: The human Val66Met polymorphism in brain-derived neurotrophic factor (BDNF), a key factor in neuroplasticity, synaptic function, and cognition, has been implicated in the pathophysiology of neuropsychiatric and neurodegenerative disorders. BDNF is encoded by multiple transcripts with distinct regulation and localization, but the impact of the Val66Met polymorphism on BDNF regulation remains unclear.

Author(s): 
Mallei, Alessandra
Baj, Gabriele
Ieraci, Alessandro
Corna, Stefano
Musazzi, Laura
Lee, Francis S.
Tongiorgi, Enrico
Popoli, Maurizio

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