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1. chinaXiv:201605.01290 [pdf]

FUS Interacts with HSP60 to Promote Mitochondrial Damage

Deng, Jianwen; Yang, Mengxue; Liu, Jianghong; Sun, Shufeng; Zhu, Li; Wu, Jane Y.; Deng, Jianwen; Yang, Mengxue; Yang, Mengxue; Chen, Yanbo; Chen, Xiaoping; Cheng, Haipeng; Li, Yang; Fushimi, Kazuo; Wu, Jane Y.; Chen, Yanbo; Xu, Qi; Chen, Yanbo; Xu, Qi; Li, Yang
Subjects: Biology >> Biophysics >> Genetics & Heredity

FUS-proteinopathies, a group of heterogeneous disorders including ALS-FUS and FTLD-FUS, are characterized by the formation of inclusion bodies containing the nuclear protein FUS in the affected patients. However, the underlying molecular and cellular defects remain unclear. Here we provide evidence for mitochondrial localization of FUS and its induction of mitochondrial damage. Remarkably, FTLD-FUS brain samples show increased FUS expression and mitochondrial defects. Biochemical and genetic data demonstrate that FUS interacts with a mitochondrial chaperonin, HSP60, and that FUS translocation to mitochondria is, at least in part, mediated by HSP60. Down-regulating HSP60 reduces mitochondrially localized FUS and partially rescues mitochondrial defects and neurodegenerative phenotypes caused by FUS expression in transgenic flies. This is the first report of direct mitochondrial targeting by a nuclear protein associated with neurodegeneration, suggesting that mitochondrial impairment may represent a critical event in different forms of FUS-proteinopathies and a common pathological feature for both ALS-FUS and FTLD-FUS. Our study offers a potential explanation for the highly heterogeneous nature and complex genetic presentation of different forms of FUS-proteinopathies. Our data also suggest that mitochondrial damage may be a target in future development of diagnostic and therapeutic tools for FUS-proteinopathies, a group of devastating neurodegenerative diseases.

submitted time 2016-05-11 Hits984Downloads681 Comment 0

2. chinaXiv:201605.01241 [pdf]

Analysis of the reptile CD1 genes: evolutionary implications

Yang, Zhi; Wang, Chunyan; Wang, Tao; Bai, Jianhui; Liu, Xuhan; Guo, Ying; Zhao, Yaofeng; Ren, Liming; Zhao, Yu; Ma, Qingwei; Ma, Qingwei; Wu, Xiaobing
Subjects: Biology >> Biophysics >> Genetics & Heredity

CD1, as the third family of antigen-presenting molecules, is previously only found in mammals and chickens, which suggests that the chicken and mammalian CD1 shared a common ancestral gene emerging at least 310 million years ago. Here, we describe CD1 genes in the green anole lizard and Crocodylia, demonstrating that CD1 is ubiquitous in mammals, birds, and reptiles. Although the reptilian CD1 protein structures are predicted to be similar to human CD1d and chicken CD1.1, CD1 isotypes are not found to be orthologous between mammals, birds, and reptiles according to phylogenetic analyses, suggesting an independent diversification of CD1 isotypes during the speciation of mammals, birds, and reptiles. In the green anole lizard, although the single CD1 locus and MHC I gene are located on the same chromosome, there is an approximately 10-Mb-long sequence in between, and interestingly, several genes flanking the CD1 locus belong to the MHC paralogous region on human chromosome 19. The CD1 genes in Crocodylia are located in two loci, respectively linked to the MHC region and MHC paralogous region (corresponding to the MHC paralogous region on chromosome 19). These results provide new insights for studying the origin and evolution of CD1.

submitted time 2016-05-11 Hits753Downloads520 Comment 0

3. chinaXiv:201605.01196 [pdf]

Epigenetic changes and functional study of HOXA11 in human gastric cancer

Cui, Yingying; Gao, Dan; Linghu, Enqiang; Guo, Mingzhou; Cui, Yingying; Zhan, Qimin; Zhan, Qimin; Chen, Runsheng; Brock, Malcolm V.; Herman, James G.
Subjects: Biology >> Biophysics >> Genetics & Heredity

Aim: To examine epigenetic changes and the function of HOXA11 in human gastric cancer (GC). Materials & methods: Seven GC cell lines, five cases of normal gastric mucosa and 112 cases primary GC samples were used in this study. Results: Expression of HOXA11 and lack of promoter region methylation were found in NCI-N87, MKN45, BGC823 and HGC27 cells. Loss of expression and complete methylation were found in AGS gastric cancer cells. Reduced expression and partial methylation were found in MGC803 and SGC7901 cells. Restoration of HOXA11 expression was induced by 5-aza-2'-deoxycytidine. HOXA11 was methylated in 81.25% (91/112) of primary GCs. The presence of methylation was associated with male gender, tumor size, tumor differentiation and lymph node metastasis (all p < 0.05). Restoration of HOXA11 expression reduced cell proliferation, invasion, migration and induced apoptosis and G2/M phase arrest. HOXA11 was found to inhibit Wnt signaling by upregulating NKD1 expression. Conclusion: Epigenetic silencing of HOXA11 promotes GC proliferation, migration and invasion through activation of Wnt signaling.

submitted time 2016-05-11 Hits763Downloads522 Comment 0

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