Structural and functional characterization of tumor suppressors TIG3 and H-REV107

• Published in: FEBS letters Vol. 589; no. 11; pp. 1179 - 1186
• Main Authors: Wei, Hejia, Wang, Lei, Ren, Xiaobai, Yu, Wenyu, Lin, Jian, Jin, Changwen, Xia, Bin
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 08-05-2015
• Subjects: C-terminal domain; Cell Death - genetics; CTD; H-REV107; HeLa Cells; Humans; N-terminal domain; NMR; NTD; Phospholipases A2, Calcium-Independent - chemistry; Phospholipases A2, Calcium-Independent - genetics; Phospholipases A2, Calcium-Independent - metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, Retinoic Acid - chemistry; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - metabolism; Solution structure; Structure-Activity Relationship; TIG3; Tumor suppressor; Tumor Suppressor Proteins - chemistry; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; CTD; NMR; H-REV107; Solution structure; TIG3; Tumor suppressor; NTD
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2015.04.002

•C-terminal domains (CTDs) of TIG3 and H-REV107 can induce cell death independently.•N-terminal domains (NTDs) of TIG3 and H-REV107 play opposite roles in regulating their CTDs.•The overall folds are quite similar for TIG3 and H-REV107 NTDs.•CTD binding regions on NTD are different for TIG3 and H-REV107.
H-REV107-like family proteins TIG3 and H-REV107 are class II tumor suppressors. Here we report that the C-terminal domains (CTDs) of TIG3 and H-REV107 can induce HeLa cell death independently. The N-terminal domain (NTD) of TIG3 enhances the cell death inducing ability of CTD, while NTD of H-REV107 plays an inhibitory role. The solution structure of TIG3 NTD is very similar to that of H-REV107 in overall fold. However, the CTD binding regions on NTD are different between TIG3 and H-REV107, which may explain their functional difference. As a result, the flexible main loop of H-REV107, but not that of TIG3, is critical for its NTD to modulate its CTD in inducing cell death.