Constitutively-active Positive Transcription Factor b (P-TEFb) prevents viral latency.

Eukaryotic cells rely on the positive transcription elongation factor b (P-TEFb) to transition RNA polymerase II (RNAPII) from a paused state to an actively transcribing mode. This complex is formed by the interaction of CDK9 with one of three cyclins: T1, T2a, or T2b. In this study, researchers created cells lacking the CycT1 subunit (CycT1-KO cells) to investigate CycT1's role in cellular transcription.

Despite no noticeable growth issues with the CycT1-KO cells, researchers observed a decrease in CDK9 levels and no compensatory increase in CycT2. This suggested that the reduced functional P-TEFb complexes were sufficient to maintain normal cell growth. Reporter gene assays revealed that NF-kappaB-dependent transcription induced by PMA was impaired in CycT1-KO cells, while AP1-dependent transactivation remained unaffected.

Additionally, transcription stimulated by JQ1, a potent P-TEFb inducer, was reduced in the CycT1-KO cells.

Biochemical analysis showed that P-TEFb complexes containing CycT1 (P-TEFb (CDK9:CycT1)) were efficiently released from 7SKsnRNP by JQ1, whereas P-TEFb (CDK9:CycT2) was unaffected by JQ1. Transcriptome analysis indicated a minor impact on steady-state transcription, but JQ1-dependent gene expression was severely diminished in CycT1-KO cells. Notably, among the top 13 JQ1-dependent genes identified in 33 cancer types, 11 were also significantly upregulated in Pancreatic Adenocarcinoma.

Taken together, these findings suggest that while both P-TEFb (CDK9:CycT1) and P-TEFb (CDK9:CycT2) regulate various genes, CycT1 plays a critical role in controlling highly inducible genes, which are also dysregulated in a specific type of cancer.