Disease relevance of Tsg101

• In summary, our results suggest that Tsg101 is required for normal cell function of embryonic and adult tissues but that this gene is not a tumor suppressor for sporadic forms of breast cancer [1].
• Tsg101 is a mouse tumor suppressor gene whose homozygous deletion produces transformation of NIH3T3 cells and leads to metastases in nude mice [2].

High impact information on Tsg101

• Tsg101 is essential for cell growth, proliferation, and cell survival of embryonic and adult tissues [1].
• Tumor susceptibility gene 101 (Tsg101) was identified in a random mutagenesis screen for potential tumor suppressors in NIH 3T3 cells [1].
• The Cre-mediated deletion of Tsg101 in primary cells demonstrated that this gene is essential for the growth, proliferation, and survival of mammary epithelial cells [1].
• Finally, the deletion of Tsg101 from primary tumor cells that express mutant p53 and that lack p21(Cip1) expression results in cell death, suggesting that additional transforming mutations during tumorigenesis do not affect the important role of Tsg101 for cell survival [3].
• Our previous studies have shown that cells conditionally deficient in Tsg101 arrested at the G(1)/S cell cycle checkpoint and died [3].

Biological context of Tsg101

• Inactivation of p53 had no influence on the deleterious phenotype, but Tsg101(-/-) cells were rescued through expression of exogenous Tsg101 [4].
• As a consequence, DNA replication was not initiated in Tsg101-deficient cells [4].
• The tumor susceptibility gene 101 (Tsg101) was originally discovered in a screen for potential tumor suppressors using insertional mutagenesis in immortalized fibroblasts [4].
• Assignment of the murine tumor susceptibility gene 101 (tsg101) and a processed tsg101 pseudogene (tsg101-ps1) to mouse chromosome 7 band B5 and chromosome 15 band D1 by in situ hybridization [5].
• The self-association of NEMO involves the C-terminal halves of the polypeptide chains containing two putative coiled-coil motifs (a CC2 and a LZ leucine zipper), a proline-rich region, and a ZF zinc finger motif [6].

Anatomical context of Tsg101

• Our results clearly demonstrate that Tsg101 is not a primary tumor suppressor in mouse embryonic fibroblasts [4].
• Additionally, endocytosed EGF receptors that are normally sorted to the lysosome are instead rapidly recycled back to the cell surface in tsg101 mutant cells [7].
• The mammalian tumor susceptibility gene tsg101 encodes the homologue of Vps23p, a class E Vps protein essential for normal membrane trafficking in the late endosome/multivesicular body of yeast [7].
• MAb CC2 was shown to detect specifically the underlying granular material of the cyst wall without binding to the limiting membrane of the parasitophorous vacuole [8].
• One antibody (CC2) appeared to recognize a differently expressed antigen depending on the parasite stage, reacting with a 40-kDa molecule in tachyzoites and a 115-kDa antigen in bradyzoites and oocysts [9].

Associations of Tsg101 with chemical compounds

• Antibody CC2 reacts with a complex glycolipid which contains a branched chain oligosaccharide terminating with alpha-galactose and alpha-fucose [10].
• OBJECTIVE: To evaluate CC2 (N, N'-dichloro-bis [2, 4, 6-trichlorophenyl] urea) in various hydrophilic and lipophilic formulations as a personnel decontaminant for sulphur mustard (SM) [11].
• RESULTS: CC2 reacted with peanut oil and neem oil, and was unstable in povidone iodine and Fuller's earth [11].

Other interactions of Tsg101

• In this new report we show that the cell cycle arrest in Tsg101-deficient cells is p53-dependent, but a null mutation of the p53 gene is unable to maintain cell survival [3].

Analytical, diagnostic and therapeutic context of Tsg101

• Using gene targeting, we generated genetically engineered mice with a floxed allele of Tsg101 [1].
• Fluorescence-activated cell sorting, proliferation assays, and Western blot analysis of crucial regulators of the cell cycle revealed that Tsg101 deficiency resulted in growth arrest at the G(1)/S transition through inactivation of cyclin-dependent kinase 2 [4].
• Upon mixing, isolated CC2 and LZ peptides associated to form a stable hetero-hexamer as shown by gel filtration and fluorescence anisotropy experiments [6].

References