In particular, ganglioside GD3 (GD3) has been identified as a lipid death effector [8], with a dual mechanism involving its interaction with mitochondria leading to activation of apoptotic pathways [9], [10] and the suppression of survival programs mediated by NF-κB activation [11], [12].
Taken together, our data indicate that depletion of dNTPs is one of the major causes of DNA damage and senescence in MYC-depleted melanoma cells and that maintaining high TS, RRM1 and RRM2 levels is important for C-MYC-dependent suppression of senescence programs in these cells.
This finding is in keeping with the high incidence of lymphoid malignancies in mouse models of Runx1 mutation (Jacob et al., 2010; Kundu et al., 2005; Putz et al., 2006) and contrasts markedly with the suppression of lymphoid programs caused by Flt3-ITDs in MPPs.
These results suggest that HFD-induced hyperleptinemia contributes to the suppression of the lipogenic program, consistent with previously reported findings that indicate the requirement of functional leptin actions for HFD-induced suppression of de novo lipogenesis using the leptin receptor-defective Zucker diabetic fatty (ZDF) rats [28], [29].
In this study, we show that in an adaptive response to overnutrition (HFD intake), the early onset of hyperleptinemia most likely contributes to the suppression of the lipogenic program in the liver and white adipose tissue; leptin exerts crucial liporegulatory functions via its metabolic control of the peripheral lipogenic pathway.
On one hand, eIF3f has been identified as a major target that accounts for MAFbx/Atrogin-1 function during skeletal muscle atrophy [25] and could explain that muscle atrophy involves a suppression of the same program of gene expression that is activated during work-induced hypertrophy or by IGF in normal growth [26].
Collectively, these data demonstrate that in response to high dietary fat intake, hyperleptinemia occurs at an early stage during the progressive accumulation of fat mass, concurrent with marked suppression of the lipogenic program in the adipose tissues as well as in the liver.
This suggests a novel function of bivalent domains: suppression of the somatic/progenitor program during late spermatogenesis.
Nodal signaling, in turn, is essential to mediate Fgf9 suppression of the meiotic program, including inhibition of Stra8 and Scp3 expression and induction of the meiotic gatekeeper Nanos2.
Nodal signaling appears to be essential in mediating Fgf9 suppression of the meiotic program, including inhibition of Stra8 and Scp3 and induction of Nanos2 expression.
