Disease relevance of Tcp1

• Multiple mutations in the t complex interact to alter profoundly the transmission ratio of t complex-bearing sperm or to cause complete sterility or semisterility [1].
• We have cloned a cDNA for the 12.3kDa polypeptide (light chain 3) and found that this protein is highly homologous to mouse Tctex1, a protein encoded by a member of the multigene family in the t complex region that is involved in male sterility and the development of the germ cells [2].
• On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks [3].
• Adult mice lacking the p53/p63 target gene Perp are not predisposed to spontaneous tumorigenesis but display features of ectodermal dysplasia syndromes [4].
• In addition, p63 has also been shown to play a role in cancer development through the differential regulation of genes with tumor suppressor function and genes involved in metastasis [5].

Psychiatry related information on Tcp1

• p51A, or TAp63gamma, a translation product of gene p51, or p63, was identified as a homolog of p53 in its primary structure and transactivating function. p53 plays a decision-making role in inducing either cell cycle arrest or apoptosis in response to DNA damage, and thereby preserves genome integrity of living cells [6].

High impact information on Tcp1

• tctex-1: a candidate gene family for a mouse t complex sterility locus [1].
• The t complex polypeptide 1 (TCP-1) is a protein of unknown function expressed in large amounts during spermatogenesis [7].
• The t complex of the mouse has an important role in male germ cell development and function [1].
• DNA sequence comparison of the Tcp-1 genes suggests that the t haplotype chromosome arose within the genus Mus more than one million years ago [8].
• The Tcp-1 gene appears to be a member of a novel gene family and shows multiple changes between the predicted amino acid sequences of TCP-1B and TCP-1A [8].

Chemical compound and disease context of Tcp1

• CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro [3].

Biological context of Tcp1

• Correlations of P < 0.00001 were found between striatal HACU and chromosome 17 markers D17Tu50 and Tcp1 [9].
• The Tcp-1 gene is located in the t-complex region of mouse chromosome 17 and on the long arm of human chromosome 6 [10].
• In the fourth recombinant (tTu3), unequal crossing-over occurred within the proximal inversion between loci D17Leh119 and D17Leh66, producing a chromosome in which the region containing loci Tcp-1, T, and D17Tu5 has been duplicated [11].
• During the isolation of a cDNA for Tcp-1 two other homologous sequences were recognized and described as Tcp-1x and Tcp-1y [12].
• These data suggest that unequal synthesis or degradation of the p63/6.9 proteins occurs during spermatogenesis [13].

Anatomical context of Tcp1

• One of these, Tcp-1 has been cloned and shown to code for a protein probably essential for acrosome formation [12].
• To determine whether p63/6.9 is a direct gene product of the T/t complex, testicular cytoplasmic RNA from mice bearing the genotypes +/+, +/t and t/t was translated in a rabbit reticulocyte-derived cell-free system, and translated products were analyzed by two-dimensional gel electrophoresis [14].
• The expression levels of CCT subunits varied among seven mouse cell lines tested but showed a close correlation with growth rate [15].
• Both the CCT protein and mRNA levels in the human promyelolytic cell HL60 decreased concomitant with growth arrest during differentiation [15].
• All the CCT subunits contain motifs that are also shared by all other known chaperonins of prokaryotes and eukaryotic organelles, and that probably relate to their common ATPase function [16].

Associations of Tcp1 with chemical compounds

• It is shown here that two genes located 3' to the murine Tcp-1 and Tcp-1x genes code for proteins highly homologous to acetyl-CoA acetyltransferases [10].
• On the other hand, the CCT complex of asynchronous cells (a mixture of various phases of cell cycle) exhibited lower alpha and delta subunit content and lower chaperone activity than that of S-phase-arrested cells obtained by excess thymidine treatment [17].
• The t-complex-encoded guanine nucleotide exchange factor Fgd2 reveals that two opposing signaling pathways promote transmission ratio distortion in the mouse [18].
• They both have the unusual codon CCT for proline at position 7, which so far has been found only in a specific set of VH genes, called the NPb family [19].
• In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT) [3].

Other interactions of Tcp1

• In the mouse, a related gene, Tcp-1x, is tightly linked to Tcp-1 [10].
• Identification of the t complex-encoded cytoplasmic dynein light chain tctex1 in inner arm I1 supports the involvement of flagellar dyneins in meiotic drive [20].
• A new phenotype mapping to the t-complex, which is designated Brachyury the Second (T2), is characterized by a slightly shortened tail in heterozygotes and homozygous failure to form an organized notochord with subsequent abnormal development of posterior somites and neural tube [21].
• Genetic mapping of the t-complex region on mouse chromosome 17 including the Hybrid sterility-1 gene [22].
• Molecular structure of Tcp-10 genes from the t complex responder locus [23].

Analytical, diagnostic and therapeutic context of Tcp1

• Sequence analysis has confirmed that a 140 bp region of homology between Tcp-1 and Tcp-1x lies in the 3' portion of both genes [12].
• It is distinguishable by two-dimensional gel electrophoresis from the acidic form of p63/6.9 (p63/6.9a), which is specified by all complete t haplotypes analyzed to date [14].
• Genomic sequences derived from the mouse t complex by a microdissection cloning technique have been used as tools to obtain high resolution genetic maps of the wild-type and t haplotype forms of the most proximal portion of chromosome 17 [24].
• Southern blot analysis indicates that there are four sequences in the human genome related to the mouse t-complex gene Tcp-1 [25].
• We studied CCT cellular distribution throughout spermatogenesis by immunofluorescence and immunoelectron microscopy [26].

References