HBP21: a novel member of TPR motif family, as a potential chaperone of heat shock protein 70 in proliferative vitreoretinopathy (PVR) and breast cancer.
A large number of tetratricopeptide repeat (TPR)-containing proteins have been shown to interact with the C-terminal domain of the 70 kDa heat-shock protein (Hsp70), especially those with three consecutive TPR motifs. The TPR motifs in these proteins are necessary and sufficient for mediating the interaction with Hsp70. Here, we investigate HBP21, a novel human protein of unknown function having three tandem TPR motifs predicted by computational sequence analysis. We confirmed the high expression of HBP21 in breast cancer and proliferative vitreoretinopathy (PVR) proliferative membrane and examined whether HBP21 could interact with Hsp70 using a yeast two-hybrid system and glutathione S-transferase pull-down assay. Previous studies have demonstrated the importance of Hsp70 C-terminal residues EEVD and PTIEEVD for interaction with TPR-containing proteins. Here, we tested an assortment of truncation and amino acid substitution mutants of Hsp70 to determine their ability to bind to HBP21 using a yeast two-hybrid system. The newly discovered interaction between HBP21 and Hsp70 along with observations from other studies leads to our hypothesis that HBP21 may be involved in the inhibition of progression and metastasis of tumor cells.
Liu
Qinghuai
Q
Lab of Reproductive Medicine, Department of Cell Biology and Medical Genetics, Nanjing Medical University, 140 Han Zhong Road, Nanjing, Jiangsu 210029, People's Republic of China. liuqh@njmu.edu.cn
Gao
Juanyu
J
Chen
Xi
X
Chen
Yuxin
Y
Chen
Jie
J
Wang
Saiqun
S
Liu
Jin
J
Liu
Xiaoyi
X
Li
Jianmin
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D050505:Mutant Proteins; D012333:RNA, Messenger; C539084:TTC36 protein, human; D005982:Glutathione Transferase