Disease relevance of Tmpo

• Here, we report nonmitotic LAP 2 beta phosphorylation sites that are phosphorylated in the native protein when purified from nuclear envelopes of mouse neuroblastoma Neuro2a cells [1].
• The A2B5 and tetanus toxin-binding cells form a network of thymic epithelial cells throughout the thymic subcapsular cortex and thymic medulla and contain thymopoietin and thymosin alpha-1 [2].
• These data provide further support for the view that myasthenia gravis is a consequence of thymic disease associated with systemic release of thymopoietin, with ensuing neuromuscular block [3].
• The number of LLT metastases was decreased by treatment with peptides (TP3 = 72, TP4 = 97, TP5[thymopoietin 32-36] = 83.1 in %) and immunosuppression produced by CY was partly restored [4].
• The effects of various doses of Thymopentin, the synthetic 5 aminoacid fragment of thymopoietin injected on d -4 and d -1 on murine host resistance to Listeria monocytogenes were tested [5].

High impact information on Tmpo

• It displayed a selectivity of action similar to that of thymopoietin itself, inducing the differentiation of T lymphocytes but not of complement receptor (CR+) B lymphocytes [6].
• Thymopoietin is a polypeptide hormone of the thymus that consists of a 49 amino acid polypeptide chain of 5562 daltons [6].
• Since this peptide had 3% activity by comparison with thymopoietin, the tertiary structure of thymopoietin may be required for optimal configuration of the active site to produce full biological activity [6].
• Our data establish that the key residues involved in the active site of thymopoietin are present within a synthetic polypeptide which constitutes a minor portion of the amino acid sequence of thymopoietin [6].
• In vivo, the pentapeptide reduced the high numbers of autologous rosette-forming cells normally present in the spleens of athymic mice; this also is a property of thymopoietin [7].

Chemical compound and disease context of Tmpo

• Thymopoietin and myasthenia gravis: neostigmine-responsive neuromuscular block produced in mice by a synthetic peptide fragment of thymopoietin [3].

Biological context of Tmpo

• It is a single-copy gene organized in 10 exons spanning approximately 22 kb, which encodes all of the described Tmpo cDNA sequences, located in the central region of mouse chromosome 10 [8].
• The possible involvement of the new growing family of Tmpo proteins in nuclear architecture and cell cycle control is discussed [8].
• Thymopoietins (Tmpos) are a group of ubiquitously expressed nuclear proteins, with sequence homology to lamina-associated polypeptide 2 (LAP2) [8].
• Five phosphorylation sites were detected by nano-electrospray mass spectrometric analysis of tryptic LAP 2 beta peptides using parent ion scans specific for phosphopeptides [1].
• The 2,514 bp fragment contains a 630 bp open reading frame that encodes for 210 aa, highly homologous to the first 220 aa of the human TP beta and TP gamma isoforms and to bovine TP [9].

Anatomical context of Tmpo

• Lamina-associated polypeptide 2 beta (LAP 2 beta), an integral protein of the inner nuclear membrane, appears to be involved in the spatial organization of the interface between nucleoplasma, lamina, and nuclear envelope [1].
• TP was also shown to be expressed in athymic and old animals, lacking a functional thymus gland [9].
• In this study we report the TP expression at the transcription level in 17 murine and rat tissues of different origins and 18 lymphoid and nonlymphoid cell lines [9].
• This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes [10].
• Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program [10].

Associations of Tmpo with chemical compounds

• Synthetic pentapeptides corresponding to residues 32-36, called thymopentin and splenopentin, reproduce biological activities of thymopoietin and splenin, respectively [11].
• Calcium-dependent effect of the thymic polypeptide thymopoietin on the desensitization of the nicotinic acetylcholine receptor [12].
• At lower concentrations (2 nM), Tpo applied on C2 myotubes simultaneously with nondesensitizing concentrations of acetylcholine results in the appearance of long closed times separating groups of openings [12].
• This product, named splenin, differs from thymopoietin only in position 34, aspartic acid for bovine thymopoietin and glutamic acid for bovine splenin [11].
• Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral, thymus-derived lymphocytes [13].

Other interactions of Tmpo

• Healthy nu/nu mice were treated daily with the thymic hormone thymopoietin or with ubiquitin, polypeptides that induce the differentiation of TL+Thy-1" cells from TL-Thy-1- precursors in vitro [14].
• Thymopoietin, a 49 amino acid polypeptide hormone of the thymus discovered by its effect on neuromuscular transmission, was later shown to induce T-cell differentiation and to affect immunoregulatory balance [11].
• This was determined in vitro by studying the effects of cytosine arabinoside, hydroxyurea, actinomycin D, camptothecin, cordycepin, cycloheximide, and puromycin on the induction by thymopoietin of thymocyte differentiation, measured by the acquisition of the differentiation allo-antigens TL and Thy-1 by and inducible fraction of mouse spleen cells [15].
• We investigated whether thymopentin, a synthetic pentapeptide derivative of thymopoietin, could enhance the protective effect of interleukin-1 alpha when both administered prior to sublethal irradiation in the C57BL/6 mouse [16].

Analytical, diagnostic and therapeutic context of Tmpo

• Further in situ hybridization studies revealed that within the thymus, the highest levels of TP mRNA are noted at the cortex [9].
• We report here the molecular cloning of a murine TP cDNA [9].
• Southern blot analysis of genomic DNA revealed that in mouse, calf and human TP is encoded by a single genomic locus [9].
• These immune deficiencies of aged mice were also reversed when old mice were treated with thymopoietin in vivo or splenocytes from old mice were incubated with thymopoietin before adoptive transfer to young irradiated, thymectomized syngeneic mice [17].
• A radioimmunoassay for thymopoietin revealed a crossreaction with a product found in spleen and lymph node but not other tissues [11].

References