Hax-1 is rapidly degraded by the proteasome dependent on its PEST sequence

BMC Cell Biology

Research Article

Erkang Fei¹  Haigang Ren²  Dong Chen²  Guanghui Wang²  Qingsong Hu³  Ranjie Xu³  Bin Li³ 

[1] Laboratory of Molecular Neuropathology and Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, 230027, Hefei, Anhui, People's Republic of China;Laboratory of Molecular Neuropathology, Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, 201203, Suzhou, Jiangsu, People's Republic of China;Laboratory of Molecular Neuropathology, Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, 201203, Suzhou, Jiangsu, People's Republic of China;Laboratory of Molecular Neuropathology and Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, 230027, Hefei, Anhui, People's Republic of China;

关键词: Hax-1;    Proteasome;    Ubiquitin;    PEST sequence;    Bcl-2 family protein;   

DOI  :  10.1186/1471-2121-13-20

 received in 2012-03-05, accepted in 2012-07-13,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHS-1-associated protein X-1 (Hax-1), is a multifunctional protein that has sequence homology to Bcl-2 family members. HAX-1 knockout animals reveal that it plays an essential protective role in the central nervous system against various stresses. Homozygous mutations in the HAX-1 gene are associated with autosomal recessive forms of severe congenital neutropenia along with neurological symptoms. The protein level of Hax-1 has been shown to be regulated by cellular protease cleavage or by transcriptional suppression upon stimulation.ResultsHere, we report a novel post-translational mechanism for regulation of Hax-1 levels in mammalian cells. We identified that PEST sequence, a sequence rich in proline, glutamic acid, serine and threonine, is responsible for its poly-ubiquitination and rapid degradation. Hax-1 is conjugated by K48-linked ubiquitin chains and undergoes a fast turnover by the proteasome system. A deletion mutant of Hax-1 that lacks the PEST sequence is more resistant to the proteasomal degradation and exerts more protective effects against apoptotic stimuli than wild type Hax-1.ConclusionOur data indicate that Hax-1 is a short-lived protein and that its PEST sequence dependent fast degradation by the proteasome may contribute to the rapid cellular responses upon different stimulations.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.