Cytokine activation of the Jak/Stat pathway is a key signaling network that controls manyhomeostatic programs required for development, differentiation and orchestrating responses topathogens. Activation of sets of early response genes by the Stat transcription factors is a keyendpoint for initiation of these numerous responses. We have made the observation that inaddition to their actions as transcription factors some Stats regulate the transcription ofmitochondria-encoded genes and ATP production. We hypothesize that mitochondria-localizedtranscription factors play an important role in adaptive responses to pathogens. Using mousemodels this proposal will examine the physiological importance of Stat regulation of mitochondrialrespiration.
Communication between different subcellular organelles is important for responses to environmental stresses such as pathogens. We have made the observation that the Stat family of nuclear transcription factors also reside within the mitochondria where they modulate energy production. This proposal will examine the contribution of mitochondrial-localized Stat3 to its well know actions in regulation of development and infection.
| Zhang, Qifang; Raje, Vidisha; Yakovlev, Vasily A et al. (2013) Mitochondrial localized Stat3 promotes breast cancer growth via phosphorylation of serine 727. J Biol Chem 288:31280-8 |
| Szczepanek, Karol; Lesnefsky, Edward J; Larner, Andrew C (2012) Multi-tasking: nuclear transcription factors with novel roles in the mitochondria. Trends Cell Biol 22:429-37 |
| Derecka, Marta; Gornicka, Agnieszka; Koralov, Sergei B et al. (2012) Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity. Cell Metab 16:814-24 |
