Human antiquitin: Structural and functional studies

Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Chemico-biological interactions (Impact Factor: 2.58). 12/2010; 191(1-3):165-70. DOI: 10.1016/j.cbi.2010.12.019
Source: PubMed


Antiquitin (ALDH7) is a member of the aldehyde dehydrogenase superfamily which oxidizes various aldehydes to form the corresponding carboxylic acids. Human antiquitin (ALDH7A1) is believed to play a role in detoxification, osmoregulation and more specifically, in lysine metabolism in which alpha-aminoadipic semialdehyde is identified as the specific, physiological substrate of the enzyme. In the present study, the structural basis for the substrate specificity was studied by site-directed mutagenesis. Kinetic analysis on wild-type human antiquitin and its mutants E121A and R301A demonstrated the importance of Glu121 and Arg301 in the binding as well as the turnover of alpha-aminoadipic semialdehyde. On the functional aspect, in addition to the already diversified physiological functions of antiquitin, the recent demonstration of its presence in the nucleus suggests that it may also play a role in cell growth and cell cycle progression. In this investigation, the expression level of antiquitin was monitored in synchronized WRL68 and HEK293 cell culture systems. It was found that the protein was up-regulated during G(1)-S phase transition. Immunofluorescence staining of the synchronized cells demonstrated an increased expression and accumulation of antiquitin in the nucleus during the G(1)-S phase transition. Knockdown of antiquitin using shRNA transfection also resulted in changes in the levels of several key cell cycle-regulating proteins.

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    • "ALDH7A1 is part of a superfamily of aldehyde dehydrogenases involved in the NAD(P)+-dependent oxidation of reactive aldehydes to carboxylic acids, as well as the metabolism of other important molecules such as tetrahydrofolate, γ-aminobutyric acid, RA, and betaine [14]. The gene is also suspected to play a role in regulation of hyperosmotic/oxidative stress and the cell cycle [19], [29], [30]. As previously noted, ALDH7A1 is unique amongst this family in that it is localized to the cytosol, nucleus, and mitochondria and is highly conserved through evolution, implying one or more essential roles in cell physiology [19]. "
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    • "Interestingly, AASDH accumulates maximally in the nucleus during the G 1 -S phase of replication, which is a time when oxidative stress is known to be most deleterious (Havens et al. 2006). However, its role in detoxification of aldehydes may not be its only function in the nucleus (Chan et al. 2011). We suggest that AASDH may also function in a similar manner to nuclear lactate dehydrogenase and glyceraldehyde-3- phosphate dehydrogenase, both of which are known to be part of the histone 2B transcription activation complex (Dai et al. 2008). "
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