共查询到20条相似文献,搜索用时 24 毫秒
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Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain. 总被引:13,自引:0,他引:13 下载免费PDF全文
D Spengler M Villalba A Hoffmann C Pantaloni S Houssami J Bockaert L Journot 《The EMBO journal》1997,16(10):2814-2825
The proliferation rate of a cell population reflects a balance between cell division, cell cycle arrest, differentiation and apoptosis. The regulation of these processes is central to development and tissue homeostasis, whereas dysregulation may lead to overt pathological outcomes, notably cancer and neurodegenerative disorders. We report here the cloning of a novel zinc finger protein which regulates apoptosis and cell cycle arrest and was accordingly named Zac1. In vitro Zac1 inhibited proliferation of tumor cells, as evidenced by measuring colony formation, growth rate and cloning in soft agar. In vivo Zac1 abrogated tumor formation in nude mice. The antiproliferative activity of Zac1 was due to induction of extensive apoptosis and of G1 arrest, which proceeded independently of retinoblastoma protein and of regulation of p21(WAF1/Cip1), p27Kip1, p57Kip2 and p16INK4a expression. Zac1-mediated apoptosis was unrelated to cell cycle phase and G1 arrest was independent of apoptosis, indicating separate control of apoptosis and cell cycle arrest. Zac1 is thus the first gene besides p53 which concurrently induces apoptosis and cell cycle arrest. 相似文献
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Liu ST Chang YL Wang WM Chung MH Lin WS Chou WY Huang SM 《The international journal of biochemistry & cell biology》2012,44(3):547-555
Zac1, a zinc-finger protein that regulates apoptosis and cell cycle arrest 1, such as p53, can induce cell-cycle arrest and apoptosis. The transactivation and coactivation functions of Zac1 may occur at non-promyelocytic leukemia nuclear body (PML-NB) sites in the presence of other PML-NB components, including ubiquitin-conjugating 9 (Ubc9). It is unclear whether post-translational modification of Zac1 by the small ubiquitin-like modifier SUMO plays a role in the coactivation functions of Zac1 for the regulation of the p21 gene. Mutagenesis experiments revealed that the two SUMO-binding lysine residues of Zac1, K237 and K424, repress the transactivation activity of Zac1. Studies using a SUMO-1 C-terminal di-glycine motif mutant that is deficient in the ability to form covalent bonds with lysines, SUMO-1 (GA), and a dominant-negative Ubc9 construct (C93S) indicated that SUMO-1 might regulate Zac1 transactivation and coactivation via a non-covalent interaction. Unlike the wild-type Zac1, which induced apoptosis, the Zac1 (K237/424R) double mutant had the ability to induce autophagy. The functional role of p21 remains to be investigated. SUMO-1 selectively suppressed the induction of the p21 gene and protein by wild-type Zac1 but not by the Zac1 (K237/424R) double mutant. Moreover, wild-type Ubc9 but not Ubc9 (C93S) further potentiated the suppression of SUMO-1 in all Zac1-induced p21 promoter activities. Our data reveal that p21 may be an important factor for the prevention of Zac1-induced apoptosis without affecting autophagosome formation. This work indicates that Zac1 functions are regulated, at least in part, via non-covalent interactions with SUMO-1 for the induction of p21, which is important for the modulation of apoptosis. 相似文献
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BATF2/SARI通过抑制p53依赖的NF-κB转录活性诱导肿瘤细胞凋亡 总被引:1,自引:0,他引:1
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Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation 总被引:20,自引:0,他引:20 下载免费PDF全文
Koumenis C Alarcon R Hammond E Sutphin P Hoffman W Murphy M Derr J Taya Y Lowe SW Kastan M Giaccia A 《Molecular and cellular biology》2001,21(4):1297-1310
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Arizti P Fang L Park I Yin Y Solomon E Ouchi T Aaronson SA Lee SW 《Molecular and cellular biology》2000,20(20):7450-7459
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