Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin-dependent cells.
Phosphorylation of Bcl-associated death protein (Bad) by erythropoietin-activated c-Jun N-terminal protein kinase 1 contributes to survival of erythropoietin-dependent cells.
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促红细胞生成素激活的 c-Jun N 末端蛋白激酶 1 磷酸化 Bcl 相关死亡蛋白 (Bad)，有助于促红细胞生成素依赖性细胞的存活。
DOI：
10.1016/j.biocel.2010.11.011
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发表时间：
2011-03
影响因子：
4
通讯作者：
Lin, Anning
中科院分区：
文献类型：
--
作者：
Deng, Hongbin;Zhang, Jingpu;Yoon, Taewon;Song, Danqing;Li, Diandong;Lin, Anning
关键词：
糖蛋白促红细胞生成素（Epo）是一种造血细胞因子，对于未成熟红细胞的红细胞存活是必需的。丝裂原活化的c-Jun N-末端激酶1（JNK 1）在红系细胞响应Epo的增殖和存活中起重要作用。然而，JNK 1激活促进红系细胞存活的确切机制尚不完全清楚。在这里，我们报告说，JNK 1是需要通过磷酸化和失活的促凋亡，Bcl-2同源结构域3（BH 3），只有Bcl-相关的死亡蛋白（坏）的Epo介导的细胞存活。在Epo撤除后，HCD 57细胞（一种鼠Epo依赖性细胞系）显示出与JNK 1活性降低相关的凋亡性细胞死亡增加。抑制JNK 1活性可促进Epo戒断诱导的细胞凋亡，但抑制组成型活性JNK 1的表达可抑制Epo戒断诱导的细胞凋亡。此外，Epo激活的JNK 1在苏氨酸201处磷酸化Bad，从而抑制Bad与抗凋亡分子特大B细胞淋巴瘤（Bcl-XL）的结合。丙氨酸取代苏氨酸201 Bad促进Epo撤退诱导的细胞凋亡。因此，我们的研究结果提供了JNK 1有助于红系细胞存活的分子机制。
The glycoprotein erythropoietin (Epo) is a hematopoietic cytokine necessary for the survival of erythrocytes from immature erythroid cells. The mitogen-activated c-Jun N-terminal kinase 1 (JNK1) plays an important role in the proliferation and survival of erythroid cells in response to Epo. However, the precise mechanism of JNK1 activation promoting erythroid cell survival is incompletely understood. Here, we reported that JNK1 is required for Epo-mediated cell survival through phosphorylation and inactivation of the pro-apoptotic, Bcl-2 homology domain 3 (BH3)- only Bcl-associated death protein (Bad). Upon Epo withdrawal, HCD57 cells, a murine Epo-dependent cell line, displayed increased apoptotic cell death that was associated with decreased JNK1 activity. Epo withdrawal-induced apoptosis was promoted by inhibition of JNK1 activity but suppressed by expression of a constitutively active JNK1. Furthermore, Epo-activated JNK1 phosphorylated Bad at threonine 201, thereby inhibiting the association of Bad with the anti-apoptotic molecule B-cell lymphoma-extra large (Bcl-XL). Replacement of threonine201 by alanine in Bad promoted Epo withdrawal-induced apoptosis. Thus, our results provide a molecular mechanism by which JNK1 contributes to the survival of erythroid cells.
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影响因子：
20.3
作者：
Nagata, Y;Nishida, E;Todokoro, K
通讯作者：
Todokoro, K
DOI：
10.1073/pnas.90.14.6849
发表时间：
1993-07-15
影响因子：
11.1
作者：
SAWYER, ST;HANKINS, WD
通讯作者：
HANKINS, WD
影响因子：
20.3
作者：
Jacobs-Helber, SM;Ryan, JJ;Sawyer, ST
通讯作者：
Sawyer, ST
影响因子：
4.8
作者：
JacobsHelber, SM;Penta, K;Sawyer, ST
通讯作者：
Sawyer, ST
影响因子：
2.6
作者：
Abutin, Randolph M.;Chen, Jingchun;Lung, Tina K.;Lloyd, Joyce A.;Sawyer, Stephen T.;Harada, Hisashi
通讯作者：
Harada, Hisashi