Initiation of transcription and translation elongation at the HIV-1 LTR

Following cellular activation or drug treatment, NFAT and NF-kB translocate to the nucleus and bind sites at the HIV-1 LTR. NFAT and NF-kB recruit p300/CBP to the LTR, resulting in acetylation of histone tails and transcriptional activation. In the case of NF-kB, proteosomal degradation of IkBa permits NF-kB translocation and displacement of the p50 homodimers. This is followed by Tat- dependent elongation in which Tat recruits the P-TEFb complex to TAR. Cdk9 phosphorylates the CTD of RNA Pol II, resulting in increased processivity. P-TEFb phosphorylates DSIF and NELF, resulting in removal of NELF from Pol II and converting DSIF into a positive elongation factor, thereby promoting productive elongation. Data nodes in blue represent HIV proteins. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3414 CPTAC Assay Portal]

在细胞激活或药物处理后，NFAT与NF-kB迁移至细胞核并绑定于HIV-1长末端重复序列（LTR）的位点。NFAT与NF-kB招募p300/CBP至LTR，导致组蛋白尾部的乙酰化以及转录激活。对于NF-kB而言，IkBa的蛋白酶体降解允许NF-kB的迁移及p50同源二聚体的置换。此后，Tat依赖的延长过程开始，其中Tat招募P-TEFb复合物至TAR。Cdk9磷酸化RNA Pol II的CTD（羧基末端结构域），从而增加其过程性。P-TEFb磷酸化DSIF和NELF，导致NELF从Pol II上移除，并将DSIF转化为正向延长因子，从而促进有效的延长。数据节点中蓝色部分代表HIV蛋白。该通路上的蛋白质均有针对的检测方法，可通过[https://assays.cancer.gov/available_assays?wp_id=WP3414 CPTAC检测门户]获得。