Disease relevance of TCP1

• Human TCP1 cDNA clones from both fibrosarcoma and B cell lines confirmed that there was a single expressed gene. mRNA transcripts of different sizes were accounted for by two different polyadenylation signals [1].
• In addition to its importance in development, T has intrigued geneticists because of its association with the mouse t-haplotype; this haplotype is a variant form of the t-complex and is characterized by transmission ratio distortion, male sterility and recombination suppression [2].
• Hereditary sensory neuropathy is caused by a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4 ) gene [3].
• Transient promoter-reporter assays in murine lung epithelial (MLE-12) cells revealed that the core CCT alpha promoter (240 bp) was observed to exhibit a 40-fold, 8-fold, and 3-fold higher level of activity compared with the simian virus 40, human cytomegalovirus, and Rous sarcoma virus promoters, respectively [4].
• Based on the specificity of the Htt-CCT1 interaction, the CCT1 substrate-binding domain may provide a versatile scaffold for therapeutic inhibitors of neurodegenerative disease [5].

Psychiatry related information on TCP1

• When t-complex polypeptide I was related to its natural and specific substrate beta 1 tubulin, the ratio was significantly decreased in the temporal, frontal, parietal cortex and in thalamus of patients with Alzheimer's disease [6].
• Sox8 maps to the t complex on mouse chromosome 17 and to human chromosome 16p13.3, a region associated with the microphthalmia-cataract syndrome CATM and the alpha-thalassemia/mental retardation syndrome ATR-16 [7].

High impact information on TCP1

• Rat monoclonal antibodies recognizing TCP-1 have been prepared and used to immunoprecipitate and Western blot a 57 kd protein from germ cell and tissue culture cell extracts [8].
• The t complex polypeptide 1 (TCP-1) is associated with the cytoplasmic aspect of Golgi membranes [8].
• The distribution in spermatids suggested that TCP-1 was localized to structures often associated with the developing acrosome [8].
• We suggest that TCP1 may represent one of a family of molecules in the eukaryotic cytosol involved in protein folding and regulated in part by their heteromeric associations [9].
• TCP1 complex is a molecular chaperone in tubulin biogenesis [10].

Biological context of TCP1

• The functional human TCP1 gene was mapped, using a panel of somatic cell hybrids, as well as in situ analysis, to the long arm of chromosome 6 at 6q23-qter and thus is not closely linked to the HLA complex on the short arm [1].
• The human TCP1 gene shared some amino acid substitutions with the mouse t-complex allele (Tcp-1a) which were not found in Tcp-1b [1].
• Nucleotide and amino-acid sequence of human testis-derived TCP1 [11].
• Genetic mapping with markers well localized cytogenetically places TCP1 and PLG proximal to TCP10 and localizes the latter to the cytogenetic band 6q27 [12].
• Assignment of the TCP1 locus to the long arm of human chromosome 6 by in situ hybridization [13].

Anatomical context of TCP1

• RESULTS: Using two-dimensional gel analysis, we have identified nine different subunits of TCP-1-containing chaperonin complexes from mammalian testis and seven different subunits of such complexes from mouse F9 cells [14].
• The 900K complex purified from reticulocyte lysate contained as its major constituent a 58K protein that cross-reacted with a monoclonal antiserum against mouse TCP1 [10].
• TCP1, the human homolog of the Tcp-1 locus in the mouse, which is part of the murine t complex and codes for an abundant testicular germ-cell protein, has been mapped within the human genome by in situ hybridization [13].
• TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix [15].
• The biological component included tumor control probability (TCP) for PTV1 (TCP1), PTV2 (TCP2), and normal tissue complication probability (NTCP) for lung, spinal cord, and heart [16].

Associations of TCP1 with chemical compounds

• Using a combination of gel filtration, ion exchange chromatography, equilibrium sucrose gradient centrifugation and immunoprecipitation, we show that the major part of cytosolic gamma-tubulin might be involved in complexes heavier than the Tcp1 particle [17].
• The CCT alpha promoter was significantly more active than the Clara cell 10, thymidine kinase, and phosphoglycerate kinase promoters [4].
• CCT alpha promoter-reporter activity, CCT alpha transcript levels, and immunoreactive protein levels increased significantly in the presence of all-trans retinoic acid [4].
• Recently, a new level of its regulation has emerged with the discovery that signals that stimulate PC synthesis recruit CCT alpha from an inactive nuclear reservoir to a functional site on the endoplasmic reticulum [18].
• Caveolin-1 phosphorylation at tyrosine residue 14 induces the dissociation of caveolin-1 from TCP-1 and activates actin folding [19].

Physical interactions of TCP1

• Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex [20].
• Caveolin-1 interacts with the chaperone complex TCP-1 and modulates its protein folding activity [19].

Other interactions of TCP1

• Our mapping data show that human T maps to 6q27 and lies between two other genes of the t-complex, TCP1 and TCP10 [2].
• The human T-complex protein 1 gene, TCP1, encodes a molecular chaperone of the chaperonin family [21].
• TCP1 and PLG do not recombine with each other and are separated from TCP10 by about 15 cM, while the corresponding mouse genes are no more than 4 cM apart [12].
• The hetero-oligomeric eukaryotic chaperonin TRiC (TCP-1-ring complex, also called CCT) interacts cotranslationally with a diverse subset of newly synthesized proteins, including actin, tubulin, and luciferase, and facilitates their correct folding [22].
• In contrast to CCT epsilon, no significant light regulation of CCT alpha was found in the mesocotyl [23].

Analytical, diagnostic and therapeutic context of TCP1

• The second part of the study describes the characterisation of seven monoclonal antibodies raised against mouse TCP-1, also known as CCT alpha, using a combination of epitope mapping and immunoblot analysis of protein extracts from different species and tissue types [24].
• A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25 was associated with schizophrenia in the Han population [25].
• Sequence analysis revealed that the carboxyl terminus of CPAP has 31.3% amino acid identity with human Tcp-10 (a t-complex responder gene product) [26].
• Direct visualization by immunofluorescence confirmed peripherally localized TCP-1 in response to heat treatment [27].
• Via indirect immunofluorescence analysis, both hsp 73 and TCP-1 localized within the centrosome in interphase and mitotic cells [28].

References