共 32 条
GCIP and SIRT6 cooperatively suppress ITGAV gene expression by modulating c-myc transcription ability
被引:0
|作者:
Huang, Yi-Ching
[1
]
Yuan, Tien-Ming
[2
,3
]
Liu, Bang-Hung
[1
]
Liang, Ruei-Yue
[1
]
Liu, Kai-Li
[4
,5
]
Chuang, Show-Mei
[1
,6
]
机构:
[1] Natl Chung Hsing Univ, Inst Biomed Sci, Taichung, Taiwan
[2] Minist Hlth & Welf, Feng Yuan Hosp, Dept Surg, Taichung, Taiwan
[3] Cent Taiwan Univ Sci & Technol, Dept Dent Technol & Mat Sci, Taichung, Taiwan
[4] Chung Shan Med Univ, Dept Nutr, Taichung, Taiwan
[5] Chung Shan Med Univ Hosp, Dept Nutr, Taichung, Taiwan
[6] Natl Chung Hsing Univ, Dept Law, Taichung, Taiwan
关键词:
HISTONE DEACETYLASE SIRT6;
LOOP-HELIX PROTEIN;
TUMOR-SUPPRESSOR;
DNA-REPAIR;
CANCER;
OVEREXPRESSION;
REPRESSION;
CARCINOMA;
BREAST;
METHYLTRANSFERASE;
D O I:
10.1016/j.jbc.2025.108314
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Grap2 and CyclinD1 interacting protein (GCIP) has been suggested to function as a tumor suppressor and acts as a transcriptional regulator that negatively controls cancer cell growth, invasion, and migration. Knockdown of GCIP reportedly enhances cancer cell migration and invasion, but no previous study has examined the mechanism(s) by which GCIP suppresses migration/invasion in cancer cells. Here, we report that cDNA microarray-based expression profiling of A549 cells without and with knockdown of GCIP reveals that the expression levels of ITGAV and ICAM-1 are negatively regulated by GCIP. In vitro co-immunoprecipitation and in vivo proximity ligation assays reveal that GCIP interacts with c-Myc. Sequence analyses reveal the presence of two c-Myc regulatory motifs (E-boxes) within the ITGAV promoter. Luciferase reporter and ChIP assays indicate that GCIP represses ITGAV transcription by interacting with c-Myc on the E-box binding sites of the ITGAV promoter region. Furthermore, GCIP interacts with SIRT6 in vitro and in vivo and cooperates with SIRT6, thereby linking its activity, to negatively regulate transcription at the E-box by modulating c-Myc transcription ability. Taken together, these findings contribute to our understanding of GCIP in tumorigenesis and identify a previously unrecognized function of GCIP: It can interact with c-Myc and SIRT6 at E-box binding sites of the ITGAV promoter region. Our data collectively reveal a regulatory network involving GCIP, SIRT6, c-Myc, and ITGAV, and suggest that function of c-Myc in cell proliferation and migration.
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页数:14
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