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It can activate mitogen-activated protein kinase (MAPK) cascades and negatively regulates MAPK activity.
It can activate NF-κB and all three classes of mitogen-activated protein (MAP) kinases including extracellular signal-related kinase (ERK 1 and ERK2, c-Jun N-terminal kinase (JNK), and p38 [ 13- 15].
It can activate osteoclasts independent of RANKL [ 21].
It can activate the potent mitogen hepatocyte growth factor (HGF encoded by Hgf) [ 21].
It can activate mast cells, lymphocytes, and eosinophils to release the Th2-related cytokines [ 4, 5].
It can activate both Smad-dependent and Smad-independent signal pathways to induce preosteolytic factors such as PTHrP [ 23].
It can activate the H-1PV P38 late promoter which governs expression of the VP gene encoding the capsid proteins (Nuesch et al, 2012).
It can activate T cells, promote angiogenesis and induce proliferation of cells, while inhibiting p53 expression and apoptosis of the same cells [ 57, 58].
It can activate all three members of the MAPK family, but p38 MAPK has been suggested to be a key molecule mediating the response of mesenchymal cells to TNF-α [ 5].
But the DNA damage induced by VP16 has been shown that it can activate the activity of p53 [11] 11].
Together with its transcriptional co-activator, YAP65, it can activate the expression of genes that serve different functions during cell differentiation and development.
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