Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An AAA protein from the dinoflagellate Gonyaulax polyedra (GpAAA) with the unusual ability to rescue the phenotype of a yeast mutant lacking G1/S phase cyclins (cln1cln2cln3) has been isolated and the mechanism of rescue was characterized. We find that GpAAA is not a cyclin and has no similarity to any known cell cycle regulators. Instead, GpAAA forms a novel and strongly supported clade with bacterial spoIIIAA proteins and an Arabidopsis gene of unknown function. Since dinoflagellates cannot be transformed, we took advantage of the powerful genetic tools available for yeast. We find that rescue of the cln1cln2cln3 phenotype does not involve an effect on the CDK-inhibitor (CKI) Sic1p, as GpAAA does not alter the sensitivity to an inducible SIC1. Instead, Northern blot analyses show that GpAAA expression increases levels of CLB5, in agreement with the observation that GpAAA is unable to rescue the quadruple mutant cln1cln2cln3clb5. We propose that the increased transcription of CLB5 may be due to a protein remodeling function of GpAAA alleviating inhibition of the transcription factor SBF. Thus, although no known equivalents to the yeast SBF have been documented in dinoflagellates, we conclude that dinoflagellates could indeed utilize GpAAA as a cell cycle regulator.
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PMID:A dinoflagellate AAA family member rescues a conditional yeast G1/S phase cyclin mutant through increased CLB5 accumulation. 1757 41

Cdc48p is a highly conserved cytosolic AAA chaperone that is involved in a wide range of cellular processes. It consists of two ATPase domains (D1 and D2), with regulatory regions at the N- and C-terminals. We have recently shown that Cdc48p regulates mitochondrial morphology, in that a loss of the ATPase activity or positive cooperativity in the D2 domain leads to severe fragmentations and aggregations of mitochondria in the cytoplasm. We have now used serial block-face scanning electron microscopy (SBF-SEM), an advanced three-dimensional (3D) electron microscopic technique to examine the structures and morphological changes of mitochondria in the yeast Saccharomyces cerevisiae. We found that mutants lacking ATPase activity of Cdc48p showed mitochondrial fragmentations and aggregations, without fusion of the outer membrane. This suggests that the ATPase activity of Cdc48p is necessary for fusion of the outer membranes of mitochondria. Our results also show that SBF-SEM has considerable advantages in morphological and quantitative studies on organelles and intracellular structures in entire cells.
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PMID:Serial block-face scanning electron microscopy for three-dimensional analysis of morphological changes in mitochondria regulated by Cdc48p/p97 ATPase. 2489 21