The protein level of the tumour-promoting factor SET is regulated by cell density
The protein level of the tumour-promoting factor SET is regulated by cell density
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DOI：
10.1093/jb/mvab125
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发表时间：
2022-03-01
影响因子：
2.7
通讯作者：
Sato，Koichi
中科院分区：
文献类型：
--
作者：
Kohyanagi，Naoki;Kitamura，Nao;Sato，Koichi
SET/I2 PP 2A是一种多功能蛋白，作为肿瘤抑制蛋白磷酸酶2A的内在抑制剂和组蛋白伴侣。在各种癌症中观察到SET水平增加;然而，潜在的分子机制仍不清楚。在本研究中，我们发现SET蛋白随着培养细胞密度的增加而积累。这种现象不仅在癌细胞系中观察到，而且在非癌细胞系中也观察到。SET mRNA水平不受细胞密度的影响。蛋白酶体抑制降低SET水平，而自噬抑制导致SET积累，表明自噬的参与。稳定SET蛋白的SETBP 1的mRNA和蛋白表达随细胞密度增加而增加。由于SETBP 1的缺失而导致的SET水平的降低在野生型细胞中比在自噬缺陷细胞中更明显。这些结果揭示了调节SET水平的潜在机制，其中增加的细胞密度诱导SETBP 1表达并保护SET免于自噬。
SET/I2PP2A is a multifunctional protein that acts as an intrinsic inhibitor of the tumour suppressor protein phosphatase 2A and as a histone chaperone. Increased SET levels have been observed in various cancers; however, the underlying molecular mechanisms remain unclear. In this study, we found that SET protein accumulates with the increasing density of cultured cells. This phenomenon was observed not only in cancer cell lines but also in non-cancer cell lines. The mRNA levels of SET were not affected by the cell density. Proteasome inhibition decreased SET levels, whereas autophagy inhibition led to SET accumulation, indicating the involvement of autophagy. The mRNA and protein expression of SETBP1, which stabilizes the SET protein, increased with cell density. The decrease in SET level due to the loss of SETBP1 was more pronounced in wild-type cells than that in autophagy-deficient cells. These results have revealed a mechanism underlying the regulation of SET level, wherein increased cell density induces SETBP1 expression and protects SET from autophagy.