|Figure: SREBP Processing and Translocation (from http://en.wikipedia.org/wiki/Srebp)|
In the Owen et al. paper, a transgenic rat is generated which puts SREBP1c under the control of a non-insulin responsive promoter, allowing for examination of the processing of SREBP1c independent of the SREBP1c promoter. Consistent with previous findings, they show that both Wortmannin and Rapamycin block processing and mRNA synthesis, but that another inhibitor LYS6K2 which is specific for S6K (a target of mTORC1) blocks only processing and not mRNA levels.
This not only suggests that S6K is the proximal effector of the PI3K-mTORC1 pathway with respect to processing, but that S6K plays no role in the transcriptional regulation. This also, for the most part, excludes a role for the SREBP -> SRE positive feedback loop, since under LYS6K conditions, SREBP cleavage is blocked but mRNA levels are unchanged. Put another way, if the SREBP positive feedback loop was important, then this would suggest that mRNA of SREBP would be reduced under all conditions in which SREBP processing is blocked.
Owen JL, Zhang Y, Bae SH, Farooqi MS, Liang G, Hammer RE, Goldstein JL, & Brown MS (2012). Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase. Proceedings of the National Academy of Sciences of the United States of America PMID: 22927400
How is SREBP Regulated by Insulin? by Dave Bridges is licensed under a Creative Commons Attribution 3.0 Unported License.