The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential role in tumor suppression, but its role in apoptosis remains unclear. Here we show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through microRNA-mediated translational repression following apoptotic stimuli than did the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the specific RNA interference increased procaspase-3 expression, leading to its activation and PARP cleavage even without apoptotic stimuli, and sensitized the cells to apoptosis. Thus, our findings provide insight into a novel mechanism for Pdcd4 as a regulator of apoptosis.

Recent studies indicate that the balance between cell survival and proapoptotic signals determines which cells commit to life or death. We have shown that the balance between follicle-stimulating hormone and prolactin determines differentiation or apoptosis in 7th generation spermatogonia during newt spermatogenesis; however, the molecular mechanisms specifying their fate are poorly understood. Here we show that the newt RNA-binding protein (nRBP) plays a critical role in determining their fate. nRBP was identified as a clone whose mRNA is decreased by prolactin, resulting in the reduction of the protein, which is otherwise expressed predominantly in the spermatogonia. nRBP protein associated with the mRNA for newt programmed cell death protein 4 (nPdcd4) at the 3-untranslated region. nRBP reduction increased nPdcd4 mRNA but decreased its protein. In a cell-free system, cytoplasmic extracts containing reduced amounts of nRBP and nPdcd4 protein induced apoptosis, whereas adding nRBP protein to the extracts blocked apoptosis. Furthermore, overexpression of nRBP protected cells from apoptosis, stabilized the chimeric transcript containing the nPdcd4 3-untranslated region, and accelerated its translation. These data suggest that, in the absence of nRBP, nPdcd4 mRNA is not stabilized and its translation is suppressed, leading to apoptosis in the spermatogonia.Multicellular organisms maintain tissue homeostasis through response of their cells to extracellular signals that either promote their proliferation and differentiation or induce their death. Evidence is accumulating that extracellular stimuli, such as growth factors and cytokines, operate via complex signal transduction networks that ultimately control cellular fates (1); however, the complete molecular mechanisms need to be elucidated.One convenient system for studying the molecular mechanisms governing cell survival and death is spermatogenesis. It is mediated not only by cell proliferation and differentiation but also by programmed cell death or apoptosis, culminating in the production of spermatozoa. Apoptosis is necessary for eliminating unwanted cells and adjusting cell numbers in multicellular organisms to ensure tissue homeostasis.In the testis of the Japanese red-bellied newt, Cynops pyrrhogaster, primary spermatogonia proliferate through seven mitotic divisions, and then in the 8th generation the spermatogonia differentiate into primary spermatocytes and initiate meiosis in the spring when the ambient temperature is high; in contrast, in the autumn when the ambient temperature is low, the spermatogonia often undergo apoptosis in the 7th generation, resulting in the cessation of spermatogenesis (2). These findings suggest the existence of molecular mechanisms regulating the fate of 7th generation spermatogonia.We have shown in vitro and in vivo that the cellular fate in the spermatogonia is mainly regulated by changes in the endogenous levels of two peptide hormones secreted from the pituitary gland as follows: follicle-stimulating hormone (FSH) 2 th...

As a part of the challenge of reducing the use of scarce rare-earth elements in magnets, a Dy-free Nd-Fe-B magnet with the remanence and coercivity of 1370 mT and 1830 kA/m, respectively, was investigated. The grain boundary was composed of mainly two phases, R 6 T 13 M and R-rich phases. The R 6 T 13 M phase formed at around 750 to 1000 K, and in that temperature range, coercivity improved and remanence decreased. By increasing the amount of grain boundary phases to 17.3 at% R addition, coercivity higher than 1990 kA/m (25 kOe) was realized.