HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation

BCL2L12 has been found to be associated with favorable prognosis in breast cancer patients while correlated with tumorigenesis of glioblastoma and colon cancer. Here, we report that BCL2L12 and its transcript variant BCL2L12A are degraded through ubiquitin-proteasome system (UPS). Interestingly, the ubiquitinations and degradations of BCL2L12 and BCL2L12A are independent of the internal lysine residues but the first N-terminal residues. In addition, HSP70 was identified to interact with BCL2L12 and BCL2L12A and protected them from ubiquitinations and degradations in mammalian cells. In summary, HSP70 protects BCL2L12 and BCL2L12A from N-terminal ubiquitination-mediated proteasomal degradation.Structured summaryMINT-7026352, MINT-7026366: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with Hsp70 (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007)MINT-7026290: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with ubiquitin (uniprotkb:P62988) by pull down (MI:0096)MINT-7026326: Hsp70 (uniprotkb:P08107) physically interacts (MI:0218) with BCL2L12A (uniprotkb:Q9HB09-2) by anti bait coimmunoprecipitation (MI:0006)MINT-7026338: BCL2L12 (uniprotkb:Q9HB09-1) physically interacts (MI:0218) with Hsp70 (uniprotkb:P08107) by anti tag coimmunoprecipitation (MI:0007)MINT-7026304: BCL2L12A (uniprotkb:Q9HB09-2) physically interacts (MI:0218) with Hsp70 (uniprotkb:P08107) by anti tag coimmunoprecipitation (MI:0007)