Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ARP4, an essential gene of Saccharomyces cerevisiae, codes for a nuclear actin-related protein. Arp4 is a subunit of several chromatin-modifying complexes and is known to be involved in the transcriptional regulation in yeast. We used a mutant strain with a single amino acid substitution (G161D) in the conserved actin fold domain to investigate the influence of Arp4 on stress and nitrogen catabolite repression genes. The deficiency of functional Arp4 caused a highly increased sensitivity towards nitrogen starvation and to the macrolide antibiotic rapamycin. We show the changes of mRNA levels of selected genes under these conditions. The upregulation of stress genes as a consequence of treatment with rapamycin was largely Msn2p/Msn4p-dependent. The sensitivity towards rapamycin indicates a participation of Arp4 in the regulation of the TOR pathway. Consistently, arp4G161D cells exhibited an affected cell cycle. Long-term cultivation, which leads to a G1 arrest in wild-type cells, provoked arrest in G2/M (more than 60%) in the mutant strain. The same effect was observed upon treatment with rapamycin, indicating an unexpected relationship of Arp4 to TOR-mediated cell cycle arrest.
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PMID:Novel regulatory properties of Saccharomyces cerevisiae Arp4. 1667 75

Nuclear Actin-Related Proteins (ARPs) and actin combine as heterodimers to bind a large helicase subunit and form a core complex essential to the assembly and function of most chromatin remodeling and modifying machines. They are the most common shared subunits of these large and diverse assemblies in eukaryotes. We recently argued that most nuclear ARPs evolved directly from actin prior to the divergence of the eukaryotic kingdoms and did not evolve from pre-existing ARPs.2 Arabidopsis plants defective in nuclear ARP4, ARP5, ARP6, or ARP7 have extreme developmental phenotypes. Our recent publication demonstrates that ARP5-defective plants are not only dwarfed and have aberrant cell sizes, but are also hypersensitive to mutagenic agents that cause double strand DNA breaks.5 In Smith et al.6 we show that ARP6-defective plants, in addition to their extreme developmental phenotypes like small organs and early flowering, present an apparent "Phosphate Starvation Response" with strong morphological and molecular phenotypes. Herein, we interpret our latest data in the light of a hypothesis stating that in addition to their roles in overcoming DNA compaction that affects basal gene expression and silencing, nuclear ARP-containing chromatin complexes exert primary epigenetic control over high-level regulatory factors.
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PMID:Nuclear actin-related proteins at the core of epigenetic control. 2122 32