NF-κB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II
NF-κB binds P-TEFb to stimulate transcriptional elongation by RNA polymerase II
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DOI：
10.1016/s1097-2765(01)00314-8
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发表时间：
2001-08-01
期刊：
影响因子：
16
通讯作者：
Peterlin, BM
中科院分区：
文献类型：
--
作者：
Barboric, M;Nissen, RM;Peterlin, BM
为了刺激HIV - 1基因的转录延伸，反式激活因子Tat将正转录延伸因子b（P - TEFb）招募到起始的RNA聚合酶II（RNAPII）。我们发现RelA对转录的激活也依赖于P - TEFb。与Tat类似，RelA在与RNA连接时可激活转录。此外，肿瘤坏死因子 - α（TNF - α）触发P - TEFb向核因子 - κB（NF - κB）调控的白细胞介素 - 8（IL - 8）基因的招募。虽然转录起始前复合物（PIC）的形成未受影响，但P - TEFb的抑制剂DRB阻止RNAPII在IL - 8基因上延伸。值得注意的是，DRB抑制使细胞对TNF - α诱导的细胞凋亡敏感。因此，NF - κB需要P - TEFb来刺激转录延伸，并且P - TEFb在调节细胞凋亡中起着意想不到的作用。
To stimulate transcriptional elongation of HIV-1 genes, the transactivator Tat recruits the positive transcription elongation factor b (P-TEFb) to the initiating RNA polymerase II (RNAPII). We found that the activation of transcription by ReIA also depends on P-TEFb. Similar to Tat, ReIA activated transcription when tethered to RNA. Moreover, TNF-alpha triggered the recruitment of P-TEFb to the NF-B-K-regulated IL-8 gene. While the formation of the transcription preinitiation complex (PIC) remained unaffected, DRB, an inhibitor of P-TEFb, prevented RNAPII from elongating on the IL-8 gene. Remarkably, DRB inhibition sensitized cells to TNF-alpha -induced apoptosis. Thus, NF-B-K requires P-TEFb to stimulate the elongation of transcription and P-TEFb plays an unexpected role in regulating apoptosis.