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

The mouse fidget mutation is an autosomal recessive mutation that renders reduced or absent semicircular canals, microphthalmia, and various skeletal abnormalities to affected mice. We previously identified the defective gene which encodes fidgetin, a new member of the ATPases associated with diverse cellular activities (AAA proteins). Here, we report on the subcellular localization of fidgetin as well as that of two closely related proteins, fidgetin-like 1 and fidgetin-like 2. Epitope-tagging and immunostaining revealed that both fidgetin and fidgetin-like 2 were predominantly localized to the nucleus, whereas fidgetin-like 1 was both nuclear and cytoplasmic. Furthermore, deletion studies identified a putative bipartite nuclear localization signal in the middle portion of the fidgetin protein. Since AAA proteins are known to form functional hetero- or homo-hexamers, we used reciprocal immunoprecipitation to examine the potential interaction among these proteins. We found that fidgetin interacted with itself and this specific interaction was abolished when either the N- or C-terminus of the protein was truncated. Taken together, our results suggest that fidgetin is a nuclear AAA-family protein with the potential to form homo-oligomers, thus representing the first step towards the elucidation of fidgetin's cellular function and the disease mechanism in fidget mutant mice.
 ...
PMID:Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice. 1570 73

Members of the AAA-ATPase (ATPases associated with diverse cellular activities) family use the energy from ATP hydrolysis to disrupt protein complexes involved in many cellular processes. Here, we report that FIGL-1 (Fidgetin-like 1), the single Caenorhabditis elegans homolog of mammalian fidgetin and fidgetin-like 1 AAA-ATPases, controls progression through mitosis in the germ line and the early embryo. Loss of figl-1 function leads to the accumulation of mitotic nuclei in the proliferative zone of the germ line, resulting in sterility owing to depletion of germ cells. Like the AAA-ATPase MEI-1 (also known as katanin), FIGL-1 interacts with microtubules and with MEL-26, a specificity factor of CUL-3-based E3 ligases involved in targeting proteins for ubiquitin-dependent degradation by the 26S proteasome. In the germ line, FIGL-1 is enriched in nuclei of mitotic cells, but it disappears at the transition into meiosis. Conversely, MEL-26 expression is low in nuclei of the mitotic zone and induced during meiosis. FIGL-1 accumulates in the germ line and spreads to the meiotic zone after inactivation of mel-26 or cul-3 in vivo. We conclude that degradation of FIGL-1 by the CUL-3MEL-26 E3 ligase spatially restricts FIGL-1 function to mitotic cells, where it is required for correct progression through mitosis.
 ...
PMID:The AAA-ATPase FIGL-1 controls mitotic progression, and its levels are regulated by the CUL-3MEL-26 E3 ligase in the C. elegans germ line. 1787 35