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.
Yang
Junwu
J
Gene Research Center, Shanghai Medical College, Fudan University, Box 103, No. 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Hong
Yi
Y
Wang
Wenzong
W
Wu
Weibing
W
Chi
Yayun
Y
Zong
Hongliang
H
Kong
Xiangfei
X
Wei
Yuanyan
Y
Yun
Xiaojing
X
Cheng
Chunming
C
Chen
Kangli
K
Gu
Jianxin
J
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