Disease relevance of TOMM40

• We previously reported that cell lines established from human carcinomas and leukemias/lymphomas expressed high levels of an intracellular membrane-bound protein, Haymaker, whereas cell lines derived from non-malignant connective tissue cells and lymphoid cells expressed low levels of this gene product [1].

High impact information on TOMM40

• A tagged ligand-cell adsorption technique revealed a 38.5-kD plasma membrane protein (p38.5) from a prototypical NK-susceptible cell line (K562) that preferentially bound to NK cells (CD3(-)CD5(-)CD16(+)) relative to T lymphocytes (CD3(+)CD5(+) CD16(-)) [2].
• Preferential interaction of a novel tumor surface protein (p38.5) with naive natural killer cells [2].
• Flow cytometry and immunoprecipitation studies of surface-labeled tumor cells demonstrated expression of p38.5 on NK-susceptible tumor cell lines (K562, MOLT-4, Jurkat), whereas p38.5 was not detected on NK-resistant tumor cell lines (A549, Raji, MDA-MB-231) [2].
• An amino acid sequence of an 11-mer internal peptide of p38.5 did not exhibit homology to known proteins [2].
• Consistent with cellular adsorption studies, the 70-kD, p38.5 binding protein was not detected on T lymphocytes [2].

Biological context of TOMM40

• Whereas the SAM(core) complex is required for the biogenesis of all beta-barrel proteins, Mdm10 and the SAM(holo) complex play a selective role in beta-barrel biogenesis by promoting assembly of Tom40 but not of porin [3].
• Sequence analyses of these cDNA clones reveal open reading frames (ORFs) that include the previously identified 11-mer peptide from purified, native p38.5 and that have identical sequences to a gene of unknown function on chromosome 19 [4].
• These experiments suggest that the p38.5 gene (Haymaker) is widely expressed in human cells of different tissue origins but that elevated expression is associated with the malignant phenotype [4].
• The predicted cDNA and amino acid sequences of PEREC1 have extensive similarity to the Caenorhabditis elegans protein, C18E9 [5].
• Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1 [5].

Anatomical context of TOMM40

• Rather, two major components from the TOM (translocase of the outer mitochondrial membrane) complex, namely TOM20 and TOM40, are important for tRNA binding at the surface of mitochondria, suggesting that they are also involved in tRNA import [6].
• Semiquantitative studies revealed a greater level of p38.5 gene transcription in malignant cell lines compared with nonmalignant cells [4].
• The mitochondrial Tom40, Tim23 and adenine nucleotide transporter (ANT) contents were not significantly different between non-preconditioned and preconditioned myocardium [7].
• Blue native polyacrylamide gel electrophoresis of digitonin-solubilized outer membranes revealed that 1C9-2 is firmly associated with TOM40 in the approximately 400-kDa complex, with a size and composition similar to those of the fungal TOM core complex [8].
• Insertion of VDAC into the outer membrane is unaffected by plugging the translocation pore with a partially translocated matrix preprotein, and mitochondria containing a temperature-sensitive mutant of Tom40 insert VDAC at the nonpermissive temperature [9].

Associations of TOMM40 with chemical compounds

• These included three loci, BAT3 (HLA-B-associated transcript 3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40 (translocase of outer mitochondrial membrane 40), for which antisense expression from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV production by >99% [10].

Other interactions of TOMM40

• One complex of approximately 400 kDa contains the receptor Tom22 and the general import pore component Tom40, the other complex of approximately 120 kDa contains the receptor Tom70 [11].
• RT-PCR and Northern blot analyses both demonstrated p38.5 gene transcripts in normal cells, nonmalignant cell lines and malignant cell lines of epithelial as well as hematopoietic origin [4].
• Nevertheless, we show that Tom40 assembly is reduced in mitochondria depleted of human Sam50 [12].

Analytical, diagnostic and therapeutic context of TOMM40

• Anti-p38.5 antibody against the 11-mer peptide encoded in exon 5 and against a 25-mer peptide encoded in exon 1 both reacted with the same protein in immunoprecipitation studies, providing further evidence of identity [4].
• Genetic identity and differential expression of p38.5 (Haymaker) in human malignant and nonmalignant cells [4].
• Dissection of the mitochondrial import and assembly pathway for human Tom40 [12].
• Significant differences in Haymaker expression, as assessed by immunohistochemistry, between malignant and normal gynecologic tissues were not observed (p = 0.27) [1].

References