GLUCOCORTICOID REGULATION OF CYCLIN D3 GENE-TRANSCRIPTION AND MESSENGER-RNA STABILITY IN LYMPHOID-CELLS
GLUCOCORTICOID REGULATION OF CYCLIN D3 GENE-TRANSCRIPTION AND MESSENGER-RNA STABILITY IN LYMPHOID-CELLS
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DOI：
10.1210/me.9.11.1500
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发表时间：
1995-11-01
影响因子：
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通讯作者：
THOMPSON, EA
中科院分区：
文献类型：
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作者：
REISMAN, D;THOMPSON, EA
糖皮质激素导致淋巴细胞G 0/G1期阻滞。这至少部分是由于G1进展因子细胞周期蛋白D3的丰度降低。当地塞米松加入到P1798小鼠T淋巴瘤细胞中时，编码细胞周期蛋白D3的mRNA（CcnD 3（1）mRNA）迅速下调。在约2小时内观察到50%的最大抑制，在4-5小时内获得75-85%的最大抑制。Cyclin D3蛋白在P1798细胞中的半衰期约为0.5h，因此Cyclin D3蛋白的丰度与CcnD 3 mRNA的丰度平行下降。糖皮质激素的作用是可逆的，CcnD 3 mRNA在地塞米松去除后2-3 h内恢复到接近对照水平。细胞周期蛋白D 0蛋白的恢复稍微更慢。数据表明糖皮质激素调节细胞周期蛋白D3 mRNA的丰度。在加入糖皮质激素后6小时内，CcnD 3的核连续转录没有显著降低，尽管在地塞米松存在下，24小时后转录被抑制超过80%，CcnD 3 mRNA在对数中期P1798细胞中非常稳定，CcnD 3 mRNA在糖皮质激素处理的细胞中的半衰期小于1 h。放线菌素D阻断糖皮质激素的作用，表明地塞米松诱导一种物质，增加CcnD 3 mRNA的周转率，CcnD 3 mRNA丰度和CcnD 3转录的调节已在G1/S界面通过胸苷阻断的细胞中进行了研究，糖皮质激素下调CcnD 3 mRNA在细胞周期进展的情况下。这一观察结果表明，糖皮质激素对细胞周期蛋白D3表达的抑制不是细胞周期停滞的继发性后果。然而，糖皮质激素对G1/S期阻滞细胞中CcnD 3的转录没有显著影响。CcnD 3转录的抑制是延迟反应，可能反映了戒断进入GO状态，而不是糖皮质激素作用的任何近端结果。CcnD 3 mRNA的不稳定似乎是糖皮质激素的直接作用，与细胞周期进程无关，并由加速CcnD 3 mRNA降解的糖皮质激素诱导蛋白介导。
Glucocorticoids cause G0/G1 arrest of lymphoid cells. This is due, at least in part, to a decrease in the abundance of the G1 progression factor, cyclin D3. The mRNA encoding cyclin D3 (CcnD3(1) mRNA) is rapidly down-regulated when dexamethasone is added to P1798 murine T lymphoma cells. Fifty percent maximum inhibition is observed within about 2 h, Maximum inhibition of 75-85% obtains within 4-5 h. Cyclin D3 protein has a half-life of about 0.5 h in P1798 cells, Consequently, the abundance of cyclin D3 protein decreases in parallel with the abundance of CcnD3 mRNA, The effects of glucocorticoids are reversible, CcnD3 mRNA returns to near control levels within 2-3 h after removal of dexamethasone. Cyclin DO protein recovers somewhat more slowly, The data indicate that glucocorticoids regulate the abundance of cyclin D3 mRNA, There is no significant decrease in nuclear run-on transcription of CcnD3 within 6 h after addition of glucocorticoids, although transcription is inhibited more than 80% after 24 h in the presence of dexamethasone, CcnD3 mRNA is very stable in mid-log phase P1798 cells, with a half-life of more than 8 h, The half-life of CcnD3 mRNA in glucocorticoid-treated cells is less than 1 h. Actinomycin D blocks the effects of glucocorticoids, suggesting that dexamethasone induces a substance that increases the turnover rate of CcnD3 mRNA, Regulation of CcnD3 mRNA abundance and of CcnD3 transcription has been studied in cells arrested at the G1/S interface by thymidine blockade, Glucocorticoids down-regulate CcnD3 mRNA in the absence of cell cycle progression. This observation indicates that glucocorticoid inhibition of cyclin D3 expression is not a secondary consequence of cell cycle arrest. However, glucocorticoids have no significant effect on transcription of CcnD3 in G1/S phase-arrested cells, Inhibition of transcription of CcnD3 is a delayed response and probably reflects withdrawal into a GO state, rather than any proximal consequence of glucocorticoid action, Destabilization of CcnD3 mRNA appears to be a direct effect of glucocorticoids, independent of cell cycle progression, and mediated by a glucocorticoid-induced protein(s) that accelerates the degradation of CcnD3 mRNA.