From N-terminal Ubiquitination-mediated Proteasomal Degradation. Of Hsp70 In The Protection Of Bcl2l12 And Bcl2l12a

BCL2L12, a newly identified member of Bcl-2 family, has been found to be associated with favorable prognosis in breast cancer patients while correlated with tumorigenesis of glioblastoma and colon cancer. It is transcriptionally regulated by many anti-tumor drugs, such as cisplatin, carboplatin and Topotecan. However, the post-translational modification and regulation of this protein has not been studied yet. Here, we report that BCL2L12 and its transcript variant BCL2L12A are nuclear proteins that are degradated through ubiquitin-proteasome system (UPS). Interestingly, the ubiquitinations and degradations of these two proteins are independent of the internal lysine residues but the first N-terminal residues. In addition, we identified HSP70 as an interacting partner of both proteins, which protected them from ubiquitination and degradation in mammalian cells. Furthermore, ectopic expression of BCL2L12A induces apoptosis through down-regulation of Bcl-2. In summary, these data suggest that HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation, and that BCL2L12A might serve as an apoptosis regulator.