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.
Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Junwu
J
Yang
Yi
Y
Hong
Wenzong
W
Wang
Weibing
W
Wu
Yayun
Y
Chi
Hongliang
H
Zong
Xiangfei
X
Kong
Yuanyan
Y
Wei
Xiaojing
X
Yun
Chunming
C
Cheng
Kangli
K
Chen
Jianxin
J
Gu
D000595:Amino Acid Sequence; D002460:Cell Line; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
C430100:BCL2L12 protein, human; D018840:HSP70 Heat-Shock Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D046988:Proteasome Endopeptidase Complex