| Title | The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin |
| Authors | Wu, Dan Liu, Jing Wu, Baiyan Tu, Bo Zhu, Weiguo Luo, Jianyuan |
| Affiliation | Peking Univ, Hlth Sci Ctr, Dept Med Genet, Beijing 100191, Peoples R China. Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China. Univ Maryland, Sch Med, Dept Med & Res Technol, Baltimore, MD 21201 USA. Peking Univ, Hlth Sci Ctr, Dept Med Genet, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | CLN3 Endoplasmic reticulum (ER) stress JNCL Tunicamycin MOLECULAR CHAPERONES OXIDATIVE STRESS PROTEIN NEURODEGENERATION APOPTOSIS ACTIVATION MITOCHONDRIAL TRAFFICKING DISORDERS INCL |
| Issue Date | 2014 |
| Publisher | 生物化学与生物物理学研究通讯 |
| Citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2014,447,(1),115-120. |
| Abstract | Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis UNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal. and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration. (c) 2014 Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/189554 |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2014.03.120 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 医学部待认领 |
