Protomer of Lens Leucine Aminopeptidase
(structure solved by Taylor et al.)

• Lysine 6 in ubiquitin is essential in order to support ubiquitin dependent degradation related cell proliferation and differentiation in lens
• Animal models, tissue culture and cell culture models have been developed to study the etiologies of cataract and AMD and these diseases have been delayed using nutritional means.
• Consuming calorie restricted diets is associated with delayed cataract in mice. Using bioinformatic approaches we have identified proteins which are differentially expressed in control animals or animals fed calorie-restricted diets.
• Cataract is due, in part, to accumulation of photooxidatively damaged proteins in the lens.
• Younger lens tissue has all the capabilities required to selectively recognize, identify and degrade oxidatively damaged and obsolete proteins via ubiquitin mediated processes.
• Ubiquitination responses are markedly altered during aging, cell division and proliferation. Aging is associated with the loss of function of cellular protein removal systems in lens. Importantly, compromised proteolytic pathways can be reactivated.
• These lens proteolytic capabilities are similar, if not identical to proteolytic capabilities that are found in most mammalian tissues and in yeast.
• The ubiquitin proteolytic pathway is regulated by cellular redox status. Redox status is determined by levels of oxidants and antioxidants, specifically glutathione and oxidized glutathione.
• Retina pigmented epithelial cells and retina photoreceptors have similar proteolytic capabilities as lenses. These may be compromised upon exposure to light and photoreactive products such as A2E.
• Not all photooxidative damage in retina is signal transduction dependent.
• There is "crosstalk" between the ubiquitin proteolytic pathway and autophagic/lysosomal proteolytic pathway.

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