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

BMC Cell Biology

Guanghui Wang¹  Dong Chen¹  Erkang Fei²  Haigang Ren¹  Ranjie Xu²  Qingsong Hu²  Bin Li² 

[1] Laboratory of Molecular Neuropathology, Department of Pharmacology, Soochow University College of Pharmaceutical Sciences, Suzhou, Jiangsu, 201203, 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, Hefei, Anhui, 230027, People's Republic of China

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

Others  :  856967
DOI  :  10.1186/1471-2121-13-20

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

【 摘 要 】

Background

HS-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.

Results

Here, 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.

Conclusion

Our 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】

   
2012 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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