Modulation of terminal deoxynucleotidyl transferase activity by thymosin

Abstract

Thymosin fraction 5, a family of acidic polypeptides isolated from bovine thymus, contains several hormonal-like factors which have been shown to influence the maturation, differentiation and functions of T-cells. Some of these peptides have been chemically defined. Two of them, thymosin alpha 1 (M.W. 3108) and thymosin beta 4 (M.W. 4982) have been sequenced. In murine systems, terminal deoxynucleotidyl transferase (TdT) has been shown to be T-cell specific and to be present primarily in the cortisone sensitive immature T-cell populations. The daily injection of thymosin fraction 5 and two of its components, thymosin beta 3 and beta 4, significantly increases TdT activity in immune suppressed mice as compared to control groups. This study indicates that thymosin can act on prothymocytes and influence the early stages of T-cell differentiation. In an in vivo system, thymosin fraction 5 and the purified peptide, thymosin alpha 1, have high activities in decreasing TdT in normal murine thymocytes after a 22-h incubation. This effect suggests that thymosin can also act on thymocytes and regulate the later biochemical processes during T-cell differentiation.

The actin binding site on thymosin β4promotes angiogenesis

“…Although its role was initially attributed to T cell differentiation (7), it later was found that thymosin β 4 binds to G-actin in a 1:1 complex that prevents monomeric G-actin from polymerizing to filamentous F-actin but supplies a pool of actin monomers inside the cells (12,13). We and others identified thymosin β 4 as an angiogenic factor with activity during HUVEC differentiation in vitro and in vivo (5,(14)(15)(16).…”

“…Thymosin β 4 , a 43 amino acid peptide, is the most abundant member of the β-thymosins, a family of highly conserved 5 kD peptides (6). Thymosin β 4 was first isolated from calf thymus and was later found in a variety of tissues and cell types as well as in malignant cells (7)(8)(9)(10)(11). By using cDNA subtractive cloning in an in vitro vessel-forming assay for angiogenesis, thymosin β 4 expression A was increased in human umbilical vein endothelial cells (HUVECs) that were plated on Matrigel compared with HUVECs plated on plastic (5).…”

Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells.

“…(34 was originally proposed solely as a thymic hormone, based on its ability to stimulate the T-lymphocyte terminal deoxynucleotidyltransferase after intraperitoneal injection into mice (13,15) and to inhibit macrophage migration at a dosage of 5-500 pM (16). However, later studies indicated that 84 is present at a relatively high abundance in several tissues (17)(18)(19) and cell lines (20,21), raising the possibility that it may also serve a more ubiquitous role.…”

Primary structure of rat thymus prothymosin alpha.

“…This peptide was reported to show many of the biological activities of thymosin fraction 5 (refs. [9][10][11][12]; for a review, see ref. 6).…”

“…Prothymosin a was characterized as a highly acidic polypeptide (pI = 3.55) containing approximately 113 amino acid residues with the thymosin a, sequence at its NH2 terminus (18). In the mouse protection test and in assays for lymphokine release, prothymosin a was found to be [10][11][12][13][14][15][16][17][18][19][20] Table 1 is shown in parentheses. The sequence of the first 20 residues is based on the composition of the peptides T1, T2, Thl, and Th2 and the published sequences of thymosin a1 (1) and thymosin a1 (16).…”