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Thymosin ␣ 1 (T␣ 1 ) and thymosin T␣ 11 (T␣ 11 ) are polypeptides with immunoregulatory properties first isolated from thymic extracts, corresponding to the first 28 and 35 amino acid residues, respectively, of prothymosin ␣ (ProT␣), a protein involved in chromatin remodeling. It has been widely supposed that these polypeptides are not natural products of the in vivo processing of ProT␣, since neither was found in extracts in which proteolysis was prevented. Here we show that a lysosomal asparaginyl endopeptidase is able to process ProT␣ to generate T␣ 1 and T␣ 11 . In view of its catalytic properties and structural and immunological analyses, this protease was identified as mammalian legumain. It selectively cleaves some of the asparaginylglycine residues in the ProT␣ sequence; specifically, Asn 28 -Gly 29 and Asn 35 -Gly 36 residues are cleaved with similar efficiency in vitro to generate T␣ 1 and T␣ 11 , respectively. By contrast T␣ 1 is the main product detected in vivo, free in the cytosol, at concentrations similar to that of ProT␣. The data here reported demonstrate that T␣ 1 is not an artifact but rather is naturally present in diverse mammalian tissues and raise the possibility that it has a functional role.

We have analyzed the RNA expression of prothymosin a (ProTa) gene during rat development in several tissues and compared it to that of two proteins related to cell proliferation: proliferating cell nuclear antigen (PCNA)/cyclin and histone H3 (H3). The expression of ProTa gene was found to be regulated in a developmental and tissue-specific manner. The mRNA levels of ProTa followed a similar time-course in liver, brain, kidney, and testis, being highly increased in the early periods of postnatal development. However, in thymus ProTa mRNA showed only moderate changes throughout development. Our findings suggest that ProTa participates in developmental processes like cell proliferation and/or differentiation.

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1. The mechanisms that control the oxidative phase of the pentose phosphate cycle in mussel hepatopancreas were investigated. 2. The effects of GSSG (oxidized glutathione) on the inhibition of glucose 6-phosphate dehydrogenase by NADPH [Eggleston & Krebs (1974) Biochem. J. 138, 425-435] extend to 6-phosphogluconate dehydrogenase. 3. The effect of GSSG on both enzymes increases as the [NADP+1]/[NADPH] ratio decreases; greater percentage deinhibition always was obtained for 6-phosphogluconate dehydrogenase. 4. Increasing concentration of GSSG increased the percentage deinhibition. This effect is more pronounced with 6-phosphogluconate dehydrogenase. 5. We confirmed the apparent imbalance between the activities of the two enzymes [sapag-Hagar, Lagunas & Sols (1973) Biochem. Biophys. Res. Commun, 50, 179-185] in the presence of 10mM-Mg2+. 6. The imbalance practically disappears when the substrate concentrations are less than saturating and Mg2+ approaches physiological concentrations. 7. The addition of GSSG at physiological concentrations allows the activities of both enzymes to be measured at high [NADPH]/[NADP+] ratios ratios and the co-operative action of GSSG and Mg2+ on the imbalance between the two enzymes to be verified. 8. The control of the activity of the two enzymes of the pentose cycle could be carried out by deinhibition of the two dehydrogenases and by the intracellular concentrations of substrates and inorganic ions.