Disease relevance of TOM1

• Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia [1].
• A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM-1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL) [1].
• In the present study, we isolated two mAbs, H11 (IgM) and H14 (IgG1), inhibitory to syncytium formation in the coculture of TOM-1 or C91/PL (both HTLV-1-positive human T-cell lines) and MOLT-4/8 (HTLV-1-negative human T-cell line) by immunizing the membrane fraction of human osteosarcoma line HOS [2].

High impact information on TOM1

• The reactivity of BP-ALL with native P190bcr-abl derived from a Ph'-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis [3].
• Amplification of the c-abl gene was not detected in the TOM-1 cells [1].
• We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells [1].
• Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes [1].
• The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement [1].

Biological context of TOM1

• We have recently shown that endofin, a FYVE domain protein associated with the early endosome, is able to recruit cytosolic TOM1 onto endosomal membranes [4].
• In initial attempts to use the chromatin immunoprecipitation technique for the identification of additional ORC sites in the human genome, we isolated a sequence close to another actively transcribed gene (TOM1) and an alphoid satellite sequence that underlies centromeric heterochromatin [5].
• In addition, the expression of the gene TOM1 (target of Myb 1), which has not previously been associated with cellular senescence, is shown to increase in senescent cells, and we demonstrate that the expression of antisense TOM1 gene in 2BS cells can delay the progress of senescence [6].
• We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells [1].
• The cytotoxic effect of Aplidin was investigated on fresh leukaemia cells derived from children with B-cell-precursor (BCP) acute lymphoblastic leukaemia (ALL) by using stromal-layer culture system and on four cell lines, ALL-PO, Reh, ALL/MIK and TOM-1, derived from patients with ALL with different molecular genetic abnormalities [7].

Anatomical context of TOM1

• This domain structure suggests that TOM1 is another member of a family of genes implicated in the trafficking regulation of growth-factor-receptor complexes that are destined for degradation in the lysosome [8].
• Endofin recruits clathrin to early endosomes via TOM1 [4].
• Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes [9].

Other interactions of TOM1

• We also show that a human paralog of TOM1 (TOM1-like gene 1) exists [8].
• In this study, we show that the GAT domains of Tom1 and Tom1L1 interact with ubiquitin and Tollip (Toll-interacting protein) [10].
• Key features of the interaction surface between the FYVE and VHS domains of Hrs, involving helices 2 and 4 of the VHS domain, are conserved in the VHS domain of Tom1, even though Tom1 does not have a FYVE domain [9].
• Characterization of tom-1 mutants suggests that TOM-1, the C. elegans ortholog of mammalian tomosyn, functions as an endogenous inhibitor of neurotransmitter secretion [11].

References