PTEN is the major negative regulator of the PI3K signaling pathway (Gil et al., 1999; Maehama and Dixon, 1998; McConnachie et al., 2003; van Diepen and Eickholt, 2008).
As the PI3K/AKT/mTOR pathway is an important signaling pathway in regulating the cellular functions, PTEN is a major negative regulator of PI3K signaling.
Autophagy is tightly regulated by several cellular signaling pathways, and the major negative regulator is the serine/threonine kinase mammalian target of rapamycin (mTOR); however, the class III PI3K/Beclin-1 positivelysitively regulates autophagy [ 12].
mTOR is activated by Akt, a downstream product of phosphatidylinositol 3-kinase (PI3K), whereas the major negative regulator of mTOR is 5′ AMP-activated protein kinase (AMPK), which regulates intracellular energy status by sensing the AMP/ATP ratio [ 13– 15].
An earlier transcriptomic study in seven OS biopsies (Patino-Garcia et al, 2009) showed up-regulation of EBF2, a known transcription factor for osteoprotegerin (OPG), a major negative regulator of osteoclastogenesis (Khosla, 2001).
One major negative regulator of the alternative pathway in human blood is complement factor H FHH FH
Here, we uncover novel secondary mutations in Suppressor of Fused (SUFU), the major negative regulator of the Hedgehog pathway.
Many cancers express high levels of the major negative regulator of p53, mouse double minute 2 (MDM2) protein.
Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8+ T cells.
To understand the mechanism by which PHGDH modulates autophagy in ECSLCs, we probed the mTOR signaling pathway, as phosphorylated mTOR (p-mTOR) is a major negative regulator of autophagy following various stress-inducing stimuli, such as energy and nutrient deprivation38.
We also considered MDM2, a major negative regulator of p53, which was over-expressed at the RNA level in our samples.
