Molecular Mechanism Of Translationally Controlled Tumor Protein (TCTP) In Regulation Of Autophagy

In the mammalian ovary, progressive activation, development, or exhaustion of primordial follicles determines reproductive success, menopause, or end of female reproductive life. However, molecular mechanisms underlying oogenesis are primarily unknown. Here, we report a proteome-wide scan for selection signatures that identify differential proteins in the ovaries of domestic pigs and their closest wild relative. Long-term artificial selection alters ovarian gene expression, primarily through transcriptional regulation. A total of38unique proteins were identified from these spots. Function analysis of the differentially expressed proteins indicated with statistical significance that the proteins differentially-expressed were mostly related to the biological processes of cytoskeleton, cellular ion homeostasis, cellular physiological processes and metabolism, chaperone, and immune response.Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes, which function in support metabolism in response to starvation and to clear damaged proteins and organelles in response to stress. Furthermore, genetic evidence supports that autophagy plays an important role in oogenesis. Here we show that translationally controlled tumor protein (TCTP) exhibits a similar expression pattern as autophagy protein LC3, mainly in the cytoplasm of granulosa and cumulus cells. In addition to up-regulating PGK1through HIF1for energy generation, TCTP up-regulates autophagy through the AMPK-ULK1pathway. Notably, both cytoplasmic and nuclear autophagy occurred in the cells. Autophagosome membrane comes from the nuclear envelope in nucleophagy. These findings add to our understanding of dynamic recycling and energy regulation for cellular homeostasis to ensure a hypoxic niche surrounding oocytes for successful oogenesis.HIF-1α is an important transcription factor which is involved in several cellular processes related to tumorigenesis. Here we show that TCTP as a novel regulator can increase the transactivation activity of HIF1, which increases transcription of VEGF. We show that TCTP can bind to β domain of VHL and competes with HIF1α, which promotes stability of HIFla. In addition, TCTP accelerates the destabilization of VHL. Thus, TCTP plays role in regulation of both VHL stability and HIF1avtivation.