To reproduce the experimentally observed phenomena in our simple model, this is due to the assumption of multistep modifications of apoptosis inducers, which are known to give rise to switch-like behavior (see Supplementary Information).
The intensity of apoptosis increased with time.
UBL modification by SUMO-1 (small ubiquitin-related modifier, also known as UBL1) has been directly linked to modification of the apoptosis pathway in ovarian tumors[31] and is known to play an important role in spermatogenesis[32].
In a study from our laboratory, we investigated the capability of melatonin (at 10 and 100 mg/kg dosages) in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes [ 61].
Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/β-catenin pathway modification of the cellular apoptosis.
Proposed mechanisms of toxicity include oxidative stress, inhibition of DNA repair, chromosomal aberrations, micronuclei formation, induction of apoptosis, modification of cellular signaling via altered activation, expression and DNA binding activity of transcription factors, epigenetic modifications resulting in aberrant gene expression, and altered phenotype of stem cell populations [ 12- 16].
Collectively, these data indicate that SSE-mediated cell death is mainly contributed by JNK activation, followed by modification of autophagy- and apoptosis-related protein expression.
Although the mechanism remains unknown at present, it is clear that the product of the gef gene induces cellular modifications that are representative of apoptosis in these tumour cells.
Thus, the induction of apoptosis or modification of angiogenic controls by normal IRF-1-driven processes provide alternative pathways influential to tumor growth control.
Alteration of stroma components can be implicated in the modification of the development and apoptosis of hematopoietic cells [ 12, 13].
