Disease relevance of TUSC2

• Myristoylation of the fus1 protein is required for tumor suppression in human lung cancer cells [1].
• A myristoylation-deficient mutant of the Fus1 protein abrogated its ability to inhibit tumor cell-induced clonogenicity in vitro, to induce apoptosis in lung tumor cells, and to suppress the growth of tumor xenografts and lung metastases in vivo and rendered it susceptible to rapid proteasome-dependent degradation [1].
• Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in the 120 kb 3p21.3 critical region contained in nested lung and breast cancer homozygous deletions [2].
• Pulmonary alveolar proteinosis (PAP) is a heterogeneous disorder of genetic or acquired etiologies [3].
• Here, we describe an expression defect of beta c in three of seven pediatric patients with PAP and in one patient with severe lung disease suspected to be PAP [3].
• Our findings show a high frequency of Fus1 protein loss and reduction of expression in lung cancer, and suggests that this reduction may play an important role in the early pathogenesis of lung squamous cell carcinoma [4].

Psychiatry related information on TUSC2

• Less S-100 protein release was associated with better neuropsychological performance, as indexed by significant correlations with the Rey Auditory Verbal Learning memory test, descending Critical Flicker Fusion thresholds, and the Hospital Anxiety and Depression rating scales, typically around r=0 [5].
• Performance on the Critical Flicker Fusion Frequency test, Choice Reaction Time, Immediate and Delayed Word Recall, and the Compensatory Tracking Task was significantly impaired by flurazepam but not by zolpidem-MR (with the exception of the Compensatory Tracking Task) or placebo [6].
• Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment [7].
• Psychomotor performance was measured using the following tests: Critical Flicker Fusion [8].
• On the 1st and 3rd days of each of the three treatment periods subjects completed a battery of psychological tests including Critical Flicker Fusion (CFFT), Choice Reaction Time (CRT), tests of memory and subjective drug effects at 1, 2, 4 and 6 h after dosing [9].

High impact information on TUSC2

• B43-PAP eliminated greater than 99.96% of blast progenitors under conditions in which only minimal inhibition of normal bone marrow progenitor cells (CFU-GM, CFU-E, CFU-MK, CFU-GEMM) was observed [10].
• Pokeweed antiviral protein (PAP) from the summer leaves of Phytolacca americana was purified and conjugated via N-succinimidyl-3-(2-pyridyldithio)propionate to 9.2.27 anti-melanoma antibody to a glycoprotein-proteoglycan complex [11].
• These results suggest that the 37,000-mol wt PAP is present only in certain cases of TTP, and is likely to be responsible for the formation of platelet thrombi in the microcirculation [12].
• METHODS: Serum PAP was retrospectively monitored in 98 patients with acute pancreatitis during their stay in the hospital [13].
• Retention of a Bean Phaseolin/Maize {gamma}-Zein Fusion in the Endoplasmic Reticulum Depends on Disulfide Bond Formation [14].

Chemical compound and disease context of TUSC2

• Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within phospholipid membranes and inhibit cell-cell Fusion. Structure-function study [15].
• As an example of pulmonary cholesterol accumulation, a known disorder of surfactant homeostasis, pulmonary alveolar proteinosis (PAP), was studied [16].
• Phosphorothioate Oligonucleotides Inhibit Human Immunodeficiency Virus Type 1 Fusion by Blocking gp41 Core Formation [17].
• 1 Fusion proteins were constructed between the human 5-HT(1A) receptor and pertussis toxin-resistant forms of both G(i1)alpha and G(o1)alpha mutated at residue(351) from cysteine to either glycine or isoleucine [18].
• By comparison, 138 +/- 12 pmol of adenine and 143 +/- 10 pmol of guanine were released from 1 microgram of HIV-1 RNA under identical treatment conditions (5 microM recombinant PAP, 4 h treatment) [19].

Biological context of TUSC2

• Other gene expression changes, including the increase of several apoptotic or anti-proliferation genes, such as GADD45A/B and TUSC2, and the decrease of a batch of phosphatase and kinase genes, may also provide further evidences in supporting the process of PSP induced apoptosis in cancer cells [20].
• FUS1 is a novel tumor suppressor gene identified in the human chromosome 3p21.3 region that is deleted in many cancers [1].
• Our results show that myristoylation is required for Fus1-mediated tumor-suppressing activity and suggest a novel mechanism for the inactivation of tumor suppressors in lung cancer and a role for deficient posttranslational modification in tumor suppressor-gene-mediated carcinogenesis [1].
• In addition, we found no evidence for FUS1 promoter region methylation [2].
• Here we report three PAP genes in the diploid Brassica rapa; the three PAPs are associated with different lipids in specific tissues [21].

Anatomical context of TUSC2

• Loss of expression or a defect of myristoylation of the Fus1 protein was observed in human primary lung cancer and cancer cell lines [1].
• In these organs PAP was localized in isolated plastid fractions [21].
• In this work, we demonstrated that recombinant Vn50 bound P. rapae hemolymph components that were recognized by antisera to Tenebrio molitor prophenoloxidase (proPO) and Manduca sexta proPO-activating proteinase (PAP) [22].
• Pokeweed antiviral protein (PAP), a 29-kD protein isolated from Phytolacca americana inhibits translation by catalytically removing a specific adenine residue from the large rRNA of the 60S subunit of eukaryotic ribosomes [23].
• In vitro translation in the presence or absence of microsomal membranes shows that PAP is synthesized as a precursor and undergoes at least two different proteolytic processing steps to generate mature PAP [24].

Associations of TUSC2 with chemical compounds

• This enzyme, designated prophenoloxidase-activating proteinase-2 (PAP-2), differs from another PAP, previously isolated from integuments of the same insect (PAP-1) [25].
• The PAP cDNA was placed under control of the galactose-inducible GAL1 promoter and transformed into Saccharomyces cerevisiae [24].
• Although GnRH-PAP conjugate protein bound specifically to and caused cell death in cells bearing the gonadotropin-releasing hormone (GnRH) receptor, we could not detect binding or cytotoxicity using two different versions of the fusion protein in receptor-positive cells [26].
• By comparison, alanine substitutions of residues (28)KD(29), (80)FE(81), (111)SR(112), (166)FL(167) that are distant from the active site did not significantly reduce the enzymatic activity of PAP [27].
• The Inhibitor of Apoptosis Protein Fusion c-IAP2{middle dot}MALT1 Stimulates NF-{kappa}B Activation Independently of TRAF1 AND TRAF2 [28].
• Co-expression of FUS1 and c-ABL in COS1 cells blocked activation of c-Abl tyrosine kinase [29].

Regulatory relationships of TUSC2

• Tetraspanins CD9 and CD81 Modulate HIV-1-Induced Membrane Fusion [30].

Other interactions of TUSC2

• A Second SNARE Role for Exocytic SNAP25 in Endosome Fusion [31].
• DC-SIGN Facilitates Fusion of Dendritic Cells with Human T-Cell Leukemia Virus Type 1-Infected Cells [32].
• UFD1L (Ubiquitin Fusion Degradation 1 Like) gene encodes for a component of a multi-complex involved in the degradation of ubiquitin fusion proteins [33].
• Expression of Variant TMPRSS2/ERG Fusion Messenger RNAs Is Associated with Aggressive Prostate Cancer [34].
• Insulin Signaling Diverges into Akt-dependent and -independent Signals to Regulate the Recruitment/Docking and the Fusion of GLUT4 Vesicles to the Plasma Membrane [35].

Analytical, diagnostic and therapeutic context of TUSC2

• Using surface-enhanced laser desorption/ionization mass spectrometric analysis on an anti-Fus1-antibody-capture ProteinChip array, we identified wild-type Fus1 as an N-myristoylated protein [1].
• Studies using RT-PCR showed that in these latter species only totally spliced transcripts of PAP are present [36].
• Gel filtration chromatography and native gel electrophoresis revealed the PAP-SPH, proPO-PAP, and SPH-proPO associations, essential for generating high Mr, active PO at the site of infection [37].
• Circular dichroism, intrinsic fluorescence and chromatographic analysis of renaturating protein suggested that the kinetic intermediate of the hPAP folding is a monomer which displays a molten globule state (R. Kuciel, A. Mazurkiewicz & W.S. Ostrowski, 1996, Int. J. Biol. Macromol. 18, 167-175) [38].
• Using fluorescence in situ hybridization, we determined that the three rat PAP genes, and the related REG gene map in the same chromosomes region, namely 4q33-->q34 [39].

References