Disease relevance of Ptma

• Transgenic overexpression of prothymosin alpha induces development of polycystic kidney disease [1].
• Also, prothymosin alpha mRNA expression correlates with that of c-myc in human colon cancer [2].
• Immunocytochemistry for one of the identified proteins, prothymosin alpha, demonstrated prominent nuclear staining in SPEM and gastritis cystica profunda [3].
• Enhancement of humoral and cellular immune responses by an oral Salmonella choleraesuis vaccine expressing porcine prothymosin alpha [4].
• Previously, we showed that murine prothymosin alpha (ProT) enhances the efficacy of a pseudorabies DNA vaccine delivered by bacterial vectors [4].

High impact information on Ptma

• Our data do not support a direct relationship between the function of prothymosin alpha and the phosphorylation of eEF-2 [5].
• To obtain a strong phosphorylated EF-2 band, we found it necessary to add PTA to cytosolic extracts from synchronized dividing cells in various phases of the cell cycle except in mitosis [6].
• Prothymosin alpha stimulates Ca2+-dependent phosphorylation of elongation factor 2 in cellular extracts [6].
• Prothymosin alpha (ProTalpha) is an acidic protein involved in cell proliferation [7].
• Prothymosin alpha was also found to be phosphorylated in proliferating murine thymocytes and HeLa cells; the phosphorylation sites were the same as in splenic lymphocytes, but the rate of phosphorylation was about 5 times lower [8].

Biological context of Ptma

• A 180-kDa protein kinase seems to be responsible for the phosphorylation of prothymosin alpha observed in proliferating cells [7].
• The prothymosin alpha gene is specifically expressed in ectodermal and mesodermal regions during early postimplantation mouse embryogenesis [9].
• Thus, although prothymosin alpha mRNA is found throughout the cell cycle, the elevated expression in G1 may be associated with an increased requirement for prothymosin alpha during the G1/S transition or the S phase of the cell cycle [10].
• This kinetics is compatible with induction of the prothymosin alpha gene by the c-myc protein (Eilers, M., Schirm, S. and Bishop, J.M. (1991) EMBO J., 10, 133-141) [10].
• Therefore, during mouse foetal development the temporal, spatial and tissue-specific expression patterns of both myc proto-oncogenes coincide with the pattern of prothymosin alpha [2].

Anatomical context of Ptma

• Depression of prothymosin alpha production in murine thymus correlates with staphylococcal enterotoxin-B-induced immunosuppression [corrected] [11].
• To gain insight into possible functions for prothymosin alpha in the proliferative cycle of lymphocytes, we examined the kinetics of prothymosin alpha mRNA expression in mitogen stimulated murine lymphocytes [10].
• Prothymosin alpha expression occurs during G1 in proliferating B or T lymphocytes [10].
• In addition, we show that the prothymosin alpha gene is active in tissues expressing specifically N-myc such as the neuronal anlage and hair follicles in skin [2].
• Phosphate half-lives in growing, mock transfected, and vector-transfected COS cells were compared with the half-life in cells transfected with the prothymosin alpha gene to determine the fate of the predominantly ectopic phosphorylated protein [12].

Associations of Ptma with chemical compounds

• Interestingly, cycling cells that were synchronized at different stages of the cycle by means of mitotic shake off after nocodazole arrest or double thymidine block did not show variations in the levels of PT-alpha mRNA when progressed synchronously through the cycle [13].
• PT-alpha mRNA induction seems to require the synthesis of proteic factor(s) since PT-alpha mRNA response to serum restoration was abolished in the presence of cycloheximide [13].
• The complete murine prothymosin alpha molecule (110 residues) except for the N-terminal methionine deduced from the cloned cDNA has been synthesized by a solid-phase method [14].

Regulatory relationships of Ptma

• Prothymosin alpha is transcribed in all tissues expressing c-myc, including brown adipose tissue, salivary gland, thymus and liver [2].

Other interactions of Ptma

• Prothymosin alpha [corrected] (ProT alpha) and thymosin beta 4 [corrected] (T beta 4) were isolated from murine thymus and characterized by microsequence analysis [11].
• PTA has also been proposed to be a target of the c-myc protooncogene [15].
• We found high PTA levels in mammary tumors arising in c-myc, c-neu, and v-ras transgenic mice [15].
• Prothymosin alpha (ProT alpha) is a highly acidic nuclear protein, once believed to have an extracellular immunoregulatory role but more recently implicated in cell proliferation and/or differentiation [9].
• 14 h after serum restoration PT-alpha mRNA was induced as had been described by others (Eschendfeldt, W. H., and Berger, S. L. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 9403-9407) [13].

Analytical, diagnostic and therapeutic context of Ptma

• Sequence analysis of its tryptic peptides revealed that the RNA-linked protein is identical to prothymosin alpha [16].
• We compared the previously reported embryonic expression pattern of the proto-oncogene c-myc and the pattern of the prothymosin alpha gene by in situ hybridization [2].
• Expression of SPEM-related transcripts was assessed by in situ hybridization and quantitative RT-PCR, as well as immunohistochemistry for prothymosin alpha [3].
• Our results thus demonstrate for the first time, to our knowledge, the effectiveness of oral DNA vaccination using S. choleraesuis as a delivery vehicle and the potential usefulness of prothymosin alpha as a DNA vaccine adjuvant [17].
• By radioimmunoassay and by Western blot, prothymosin alpha was detected in the mouse lung [18].

References