Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells

被引：11

作者：

Cai, Bi-He ^{[1
,2
]}

Wu, Po-Han ^{[1
]}

Chou, Chi-Kan ^{[1
]}

Huang, Hsiang-Chi ^{[1
,3
,4
]}

Chao, Chia-Chun ^{[1
,5
]}

Chung, Hsiao-Yu ^{[1
]}

Lee, Hsueh-Yi ^{[1
]}

Chen, Jang-Yi ^{[2
]}

Kannagi, Reiji ^{[1
]}

机构：

[1] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[2] Natl Def Med Ctr, Dept Biol & Anat, Taipei, Taiwan

[3] Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med, Taipei, Taiwan

[4] Acad Sinica, Taipei, Taiwan

[5] Acad Sinica, Genom Res Ctr, Taipei, Taiwan

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR PROTEIN; COLORECTAL-CANCER; SIALIDASE NEU4; PSA-NCAM; TRANSCRIPTION FACTORS; DOWN-REGULATION; SIALYL-LEWIS; EXPRESSION; P53;

D O I：

10.1038/s41598-018-37521-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

More than 50% of colon cancers bear mutations in p53, one of the most important tumor suppressors, and its family members p63 or p73 are expected to contribute to inhibiting the progression of colon cancers. The AP2 family also acts as a tumor suppressor. Here we found that p73 and AP2 are able to activate NEU4, a neuraminidase gene, which removes the terminal sialic acid residues from cancerassociated glycans. Under serum starvation, NEU4 was up-regulated and one of the NEU4 target glycans, sialyl Lewis X, was decreased, whereas p73 and AP2 were up-regulated. Sialyl Lewis X levels were not, however, decreased under starvation conditions in p73-or AP2-knockdown cells. p53 and AP2 underwent protein-protein interactions, exerting synergistic effects to activate p21, and interaction of p53 with AP2 was lost in cells expressing the L350P mutation of p53. The homologous residues in p63 and p73 are L423 and L377, respectively. The synergistic effect of p53/p63 with AP2 to activate genes was lost with the L350P/L423P mutation in p53/p63, but p73 bearing the L377P mutation was able to interact with AP2 and exerted its normal synergistic effects. We propose that p73 and AP2 synergistically activate the NEU4 promoter in colon cancer cells.

引用

页数：13