1,721,083 research outputs found
Death Receptor-Induced Activation of Initiator Caspase 8 Is Antagonized by Serine/Threonine Kinase PAK4
Normal cell growth requires a precisely controlled balance between cell death and survival. This involves activation of different types of intracellular signaling cascades within the cell. While some types of signaling proteins regulate apoptosis, or programmed cell death, other proteins within the cell can promote survival. The serine/threonine kinase PAK4 can protect cells from apoptosis in response to several different types of stimuli. As is the case for other members of the p21-activated kinase (PAK) family, one way that PAK4 may promote cell survival is by phosphorylating and thereby inhibiting the proapoptotic protein Bad. This leads in turn to the inhibition of effector caspases such as caspase 3. Here we show that in response to cytokines which activate death domain-containing receptors, such as the tumor necrosis factor and Fas receptors, PAK4 can inhibit the death signal by a different mechanism. Under these conditions, PAK4 inhibits apoptosis early in the caspase cascade, antagonizing the activation of initiator caspase 8. This inhibition, which does not require PAK4's kinase activity, may involve inhibition of caspase 8 recruitment to the death domain receptors. This role in regulating initiator caspases is an entirely novel role for the PAK proteins and suggests a new mechanism by which these proteins promote cell survival
L'economia e la politica monetaria
Il volume intende rispondere al quesito "se e come la moneta influenza le relazioni economiche", attraverso la descrizione del quadro finanziario e produttivo dell'economia, la comprensione delle decisioni monetarie dei macro-operatori economici, l'analisi dei processi che determinano gli equilibri macroeconomici e la descrizione dei meccanismi utilizzati nei paesi istituzionalmente avanzati per raggiungere gli obiettivi indicati dalle banche centrali
Plant Flowering : Imposing DNA Specificity on Histone-Fold Subunits
CONSTANS (CO) is a master regulator of flowering time, although the mechanisms underlying its role as a transcriptional regulator are not well understood. The DNA-binding domain of CO shares homology with that of NUCLEAR FACTOR YA (NF-YA), a subunit of the CCAAT-binding trimer NF-Y. Recent publications indicate that CO and its rice homolog HEADING DATE 1 (Hd1) form heterotrimers with the histone-fold subunits of NF-Y to efficiently bind promoter elements in the florigen genes. Differences in the DNA-binding specificities of NF-Y and NF-CO can be conceptualized based on our knowledge of the 3D structure of the NF-Y/. CCAAT complex. Here we discuss the modes of assembly of NF-Y-like heterotrimers and possible models for their activity as flexible sequence-specific transcriptional regulators
La grotta di Settecannelle: L’Epigravettiano
Il contributo presenta l'analisi tecno-funzionale delle industrie litiche Epigravettiane rinvenute all'interno della Grotta di Settecannell
Analisi tipologica e funzionale delle punte à cran epigravettiane della Grotta delle Settecannelle (Viterbo)
Tra il 19.000 e il 14.000 BP, nelle culture europee del Paleolitico
Superiore, si assiste a una generale diffusione di punte e lame con
un incavo laterale (cran) ottenuto con ritocco erto profondo. L’ubiquità
di questo fenomeno ha portato molti studiosi (Plisson,
Geneste 1989; Onoratini 1978; Lansac 2004) a considerarlo come
il riflesso di nuove tecniche di caccia, conseguenti l’invenzione di
strumenti che permettevano di lanciare con maggior forza un proiettile
e di colpire la preda da maggiore distanza. Frecce, giavellotti,
zagaglie venivano scagliati con propulsori, bastoni muniti di un
gancio o di un incavo nel quale si appoggiava l’arma da lanciare,
oppure con archi
The serine/threonine kinase PAK4 prevents caspase activation and protects cells from apoptosis
The serine/threonine kinase PAK4 was identified first as an effector molecule for the Rho GTPase Cdc42. PAK4 differs from other members of the PAK family both in sequence and function. Previously we have shown that an important function of this kinase is to mediate the induction of filopodia in response to activated Cdc42. Studies with a, constitutively active PAK4 mutant have shown that it also has a role in promoting anchorage-independent growth, an important hallmark of oncogenic transformation. Here we show that another function of PAK4 is to protect cells against apoptotic cell death. Expression of wild-type or constitutively active PAK4 delays the onset of apoptosis in response to tumor necrosis factor LY stimulation, UV irradiation, and serum starvation. Consistent with an antiapoptotic function, expression of PAK4 leads to an increase in phosphorylation of the proapoptotic protein Bad and an inhibition of caspase activation
The NF-Y/p53 liaison: Well beyond repression.
NF-Y is a sequence-specific transcription factor - TF - targeting the common CCAAT promoter element. p53 is a master TF controlling the response to stress signals endangering genome integrity, often mutated in human cancers. The NF-Y/p53 - and p63, p73 - interaction results in transcriptional repression of a subset of genes within the vast NF-Y regulome under DNA-damage conditions. Recent data shows that NF-Y is also involved in pro-apoptotic activities, either directly, by mediating p53 transcriptional activation, or indirectly, by being targeted by a non coding RNA, PANDA. The picture is subverted in cells carrying Gain-of-function mutant p53, through interactions with TopBP1, a protein also involved in DNA repair and replication. In summary, the connection between p53 and NF-Y is crucial in determining cell survival or death
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