Disease relevance of Tnp1

• Recently, we showed that EBNA-2 interacts with the TP1 promoter of EBV through a cellular protein [1].
• Mesenchymal-to-Epithelial Transition Facilitates Bladder Cancer Metastasis: Role of Fibroblast Growth Factor Receptor-2 [2].
• In vitro growth of Mycobacterium lepraemurium: Transition from in vivo grown to in vitro adaptation [3].
• Soluble TNF Mediates the Transition from Pulmonary Inflammation to Fibrosis [4].

High impact information on Tnp1

• Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail [5].
• In step 12 to 16 spermatid nuclei from Tnp2-null mice, there was normal displacement of histones, a compensatory translationally regulated increase in TP1 levels, and elevated levels of precursor and partially processed forms of P2 [6].
• (2) Transition of a premutation allele to full mutation occurs in a postzygotic stage after separation of the germ line and is restricted to soma cells (restriction hypothesis) [7].
• The genes encoding three different mammalian testis-specific nuclear chromatin proteins, mouse transition protein 1, mouse protamine 1, and mouse protamine 2, all of which are expressed postmeiotically, are marked by methylation early during spermatogenesis in the mouse [8].
• Analysis of DNA from the testes of prepubertal mice and isolated testicular cells revealed that transition protein 1 became progressively less methylated during spermatogenesis, while the two protamines became progressively more methylated; in contrast, the methylation of beta-actin, a gene expressed throughout spermatogenesis, did not change [8].

Biological context of Tnp1

• Nucleoprotein transitions during spermiogenesis in mice with transition nuclear protein Tnp1 and Tnp2 mutations [9].
• Epididymal sperm from the nine possible Tnp1 and Tnp2 null genotypes demonstrated a general decrease in normal morphology, motility, chromatin condensation, and degree of protamine 2 processing with decreasing levels of transition proteins in mutant sperm [10].
• Comparison of the nucleotide sequences for Stp-1 and the mouse gene coding for protamine P1 suggests a possible evolutionary relationship [11].
• The mouse transition protein 1 gene contains a B1 repetitive element and is located on chromosome 1 [12].
• We also show that sequences similar to Prot1C are found in the promoter region of other testis-specific genes, such as the transition protein 1-encoding gene promoter which is thought to have derived from the P1 genes [13].

Anatomical context of Tnp1

• It is believed that the transition proteins (Tnp1 and Tnp2) participate in the removal of the nucleohistones and in the initial condensation of the spermatid nucleus [14].
• Serial sections of rat testis exposed separately to antisera to TP1 and TP2 showed that the great majority of labeled tubules were reactive to both antisera [15].
• Southern blot hybridization to genomic DNA isolated from a panel of mouse-hamster somatic cell hybrids unambiguously mapped Stp-1 to mouse chromosome 1 [11].
• Our results reveal at least four additional forms of translational control over these mRNAs: (1) The vast majority of the active forms of the transition protein 1 mRNA and both protamine mRNAs sediment with polysomes in which the ribosomes are spaced closer than is typical of mammalian mRNAs (31-38 vs 80-100 bases apart) [16].
• Two kinds of active protein fraction, TP1 and TP2, were isolated from bovine thymus extracts [17].

Associations of Tnp1 with chemical compounds

• Experiments conducted with two fragments of TP1 containing arginine and lysine residues demonstrated that DNA binding by TP1 must involve more than these basic sequences [18].
• Cyclosporin, an inhibitor of the mitochondrial Permeability Transition, PT, restored normal respiration rates to lymphocytes from old mice, suggesting enhanced susceptibility to PT activation [19].

Other interactions of Tnp1

• Abnormalities and reduced reproductive potential of sperm from Tnp1- and Tnp2-null double mutant mice [10].
• Tp-1 mapped 0.8 +/- 0.8 cM proximal and Sag 12.8 +/- 1.7 cM distal to (Vil,Bcg) [20].
• The proximal deletion breakpoint maps within the 0.8-cM segment separating Tp1 and Vil [21].
• The maximum size of the Spr deletion is estimated to be 16 cM, the genetic distance between Tp1 and Acrg [21].
• Mice defective in spermiogenesis (Tnp1(-/-), Gmcl1(-/-), Asm(-/-)) showed wild-type mid-preleptotene and bouquet frequencies [22].

Analytical, diagnostic and therapeutic context of Tnp1

• Isoelectric focusing showed the isoelectric point at pH 5.65 for TP1 and pH 5.4 for TP2 [17].
• To identify the cellular protein interacting with the TP1 promoter, we performed electrophoretic mobility shift assays using binding sequences of known transcription factors, that carry partial homology to the crucial sequences of the EBNA-2 responsive element (EBNA-2RE), as competitor [1].

References