%0 Journal Article
%T Hax-1 is rapidly degraded by the proteasome dependent on its PEST sequence
%A Li Bin
%A Hu Qingsong
%A Xu Ranjie
%A Ren Haigang
%J BMC Cell Biology
%D 2012
%I BioMed Central
%R 10.1186/1471-2121-13-20
%X 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.
%K Hax-1
%K Proteasome
%K Ubiquitin
%K PEST sequence
%K Bcl-2 family protein
%U http://www.biomedcentral.com/1471-2121/13/20