Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-terminal (Nt) acetylation (NTA) is an ample and irreversible cotranslational protein modification catalyzed by ribosome-associated Nt-acetyltransferases. NTA on specific proteins can act as a degradation signal (called an Ac/N-degron) for proteolysis in yeast and mammals. However, in plants, the biological relevance of NTA remains largely unexplored. In this study, we reveal that Arabidopsis (Arabidopsis thaliana) SIGMA FACTOR-BINDING PROTEIN1 (SIB1), a transcription coregulator and a positive regulator of salicylic acid-primed cell death, undergoes an absolute NTA on the initiator Met; Nt-acetyltransferase B (NatB) partly contributes to this modification. While NTA results in destabilization of certain target proteins, our genetic and biochemical analyses revealed that plant NatB-involved NTA instead renders SIB1 more stable. Given that the ubiquitin/proteasome system stimulates SIB1 degradation, it seems that the NTA-conferred stability ensures the timely expression of SIB1-dependent genes, mostly related to immune responses. Taking our findings together, here we report a noncanonical NTA-driven protein stabilization in land plants.
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PMID:N-Terminal Acetylation Stabilizes SIGMA FACTOR BINDING PROTEIN1 Involved in Salicylic Acid-Primed Cell Death. 3238 85

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer andaccounts for 85% of all lung carcinomas. The hepatocyte growth factor receptor (c-Met) hasbeen considered a potential therapeutic target for NSCLC. Proteasome inhibition induces cellapoptosis and has been used as a novel therapeutic approach for treating diseases includingNSCLC; however, the effects of different proteasome inhibitors on NSCLC have not beenfully investigated. The aim of this study is to determine a precise strategy for treating NSCLCby targeting c-Met using different proteasome inhibitors. Three proteasome inhibitors,Bortezomib, MG132, and ONX 0914, were used in this study. Bortezomib (50 nM)significantly reduced c-Met levels and cell viability in H1299 and H441 cells, while similareffects were observed in H460 and A549 cells when a higher concentration (~100 nM) wasused. Bortezomib decreased c-Met gene expression in in H1299 and H441 cells, but it hadno effect in A549 and H460 cells. MG-132 at a low concentration (0.5 uM) diminished c-Met levels in H441 cells, while neither a low nor high concentration (~20 uM) altered c-Metlevels in A549 and H460 cells. A higher concentration of MG-132 (5 uM) was required fordecreasing c-Met levels in H1299 cells. Furthermore, MG-132 induced cell death in all fourcell types. Among all four cell lines, H441 cells expressed higher levels of c-Met andappeared to be the most susceptible to MG-132. MG-132 decreased c-Met mRNA levels inboth H1299 and H441 cells. ONX 0914 reduced c-Met levels in H460, H1299, and H441cells but not in A549 cells. c-Met levels were decreased the most in H441 cells treated withONX 0914. ONX 0914 did not alter cell viability in either H441, however, it did induce celldeath among H460, A549, and H1299 cells. This study reveals that different proteasomeinhibitors produce varied inhibitory effects in NSCLS cell lines.
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PMID:Proteasome inhibitors diminish c-Met expression and induce cell death in non-small cell lung cancer cells. 3258 Aug 19


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