Akt activation enhances ribosomal RNA synthesis through casein kinase II and TIF-IA

作者：Le Xuan Truong Nguyen; Mitchell Beverly S^*

来源：Proceedings of the National Academy of Sciences, 2013, 110(51): 20681-20686.

DOI：10.1073/pnas.1313097110

• PKB/Akt
• acute myelogenous leukemia

Transcription initiation factor I (TIF-IA) plays an essential role in regulating ribosomal RNA (rRNA) synthesis by tethering RNA polymerase I (Pol I) to the rDNA promoter. We have found that activated Akt enhances rRNA synthesis through the phosphorylation of casein kinase II alpha (CK2 alpha) on a threonine residue near its N terminus. CK2 in turn phosphorylates TIF-IA, thereby increasing rDNA transcription. Activated Akt also stabilizes TIF-IA, induces its translocation to the nucleolus, and enhances its interaction with Pol I. Treatment with AZD8055, an inhibitor of both Akt and mammalian target of rapamycin phosphorylation, but not with rapamycin, disrupts Akt-mediated TIF-IA stability, translocation, and activity. These data support a model in which activated Akt enhances rRNA synthesis both by preventing TIF-IA degradation and phosphorylating CK2 alpha, which in turn phosphorylates TIF-IA. This model provides an explanation for the ability of activated Akt to promote cell proliferation and, potentially, transformation.

• 出版日期2013-12-17