Disease relevance of IFITM1

• Expression of IFITM1 in chronic myeloid leukemia patients [1].
• Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene [2].
• The overexpression of 9-27 in the gastric cancer cells rendered tumor cells more resistant to natural killer cells [3].
• Partial inhibition of vesicular stomatitis virus by the interferon-induced human 9-27 protein [4].
• Four patients had undergone surgical repair of tetralogy of Fallot, and 3 had surgical correction of double outlet of the right ventricle at the mean age of 18 +/- 7 years (range, 9-27 years) before documentation of the arrhythmia [5].

High impact information on IFITM1

• The rat gene homologous to the human gene 9-27 is involved in the development of the mammary gland [6].
• By using the subtractive cDNA library approach, we isolated a cDNA that is highly expressed in the dome-forming cells, and identical to the rat8 gene and highly homologous to the human 9-27 gene [6].
• Furthermore, the 9-27 (GGAAATAGAAACT) and 6-16 (GGGAAAATGAAACT) ISREs can each confer a response to both types of IFN when placed on the 5' side of a marker gene [7].
• Analysis of constructs containing native and mutated ISREs suggests that this motif is essential for the response of 9-27 to IFN-gamma as well as IFN-alpha [7].
• These profiles showed many similarities to reported interferon-gamma-induced gene expression in normal CD34+ cells; indeed the 2 most up-regulated genes, IFIT1 and IFITM1, are interferon-stimulated genes (ISGs) [8].

Biological context of IFITM1

• IFITM1 is a component of a multimeric complex involved in the trunsduction of antiproliferative and cell adhesion signals [1].
• Expression level of IFITM1 was found significantly different between the high- and low-risk groups (P = 9.7976 x 10(-11)) by real-time reverse transcription polymerase chain reaction (RT-PCR) [1].
• The present results suggest a novel role of LEU13 different from that in the inhibition of cell proliferation, involved in IFNA-induced refractoriness of RSa cells to X rays [9].
• Overexpression of IFITM1 negatively regulated cell growth, whereas suppression of IFITM1 blocked the antiproliferative effect of IFN-gamma, accelerated the cell growth rate and conferred tumorigenicity to a non-malignant hepatocyte in nude mice [10].
• Moreover, substitution of Ala for Leu12, Val20, Leu21, Phe31, Leu33, or Leu39 and replacement of Leu13 with Ile or Val did not impair the dimerization reaction [11].

Anatomical context of IFITM1

• LEU13, a leukocyte surface protein, was previously reported to mediate the actions of IFN such as inhibition of cell proliferation [9].
• The interferon-inducible 9-27 gene modulates the susceptibility to natural killer cells and the invasiveness of gastric cancer cells [3].
• Among the genes identified, 9-27 gene was highly expressed in gastric tumor tissues and in cancer cell lines [3].
• The highly conserved interferon (IFN)-stimulated regulatory elements of the human genes 6-16 and 9-27 bind to one or more proteins (E factor) detected in extracts of human Bristol 8 B cells or human foreskin fibroblast cells treated with IFN-alpha [12].
• The high inhibitory potency of the previously developed bombesin antagonist [Leu13, psi CH2NHLeu14]bombesin (analogue I) (IC50 values of 30 and 18 nM for inhibition of bombesin-stimulated amylase secretion from guinea pig acinar cells and Swiss 3T3 cell growth, respectively) diminished considerably when shorter chain lengths were examined [13].

Associations of IFITM1 with chemical compounds

• In 2 genes (IFITM1, 6-16), the response to IFN-alpha could be restored by treatment with lamivudine [14].
• Although TPA can mimic the effect of interferon on cell differentiation, it does not induce 2'5' oligoadenylate synthetase or the interferon-sensitive mRNAs, 6-16 or 9-27 [15].
• Instead, several amino acid substitutions, including Leu13/Arg18, Phe111/Arg114, Asp174/Val181, and Phe285/His294 (human/potato), provide side chains that mimic the role of putrescine in the human enzyme [16].
• We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN) [17].
• A plasmid construct was prepared (pISRELuc) which contains four tandem repeats of 9-27 ISRE sequences positioned directly upstream of the herpes virus 1 thymidine kinase promoter TATA box that drives the expression of firefly luciferase [18].

Physical interactions of IFITM1

• Evidently, large hydrophobic side chains of Leu13 and Phe36 play pivotal roles in stabilizing RII beta-RII beta interactions [11].

Regulatory relationships of IFITM1

• IFN-gamma and IFN-alpha induce the expression and synthesis of Leu 13 antigen by cultured human endothelial cells [19].

Other interactions of IFITM1

• TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen [20].
• The levels of endogenous mRNA of two interferon-stimulated genes, 6-16 and 9-27, were increased in cells containing increased levels of IRF-1 [21].
• Although many genes did respond to IFN-gamma in U2, the 9-27 gene did not and the antiviral response of U2 cells to IFN-gamma was greatly reduced [22].
• Substitution of Ala for Leu13 or Phe36 generates monomeric RII beta subunits that cannot bind AKAP75 [11].
• Levels of CD21 were decreased, whereas levels of CD81 and CD225 were normal, in all four patients [23].

Analytical, diagnostic and therapeutic context of IFITM1

• Sequence analysis of a full-length cDNA clone revealed identity with the 9-27 cDNA, previously isolated on the basis of its interferon inducibility by differential screening [24].
• For bilayers aligned with the normal along the applied magnetic field there was no shift in the carbonyl resonances of residues Ile2, Ala4, Leu9, Leu13, or Ala15, with minor changes for residues Val8 and Ile20, and small changes at Val5, Leu6 and Ile17 on immobilization of the peptide below Tc [25].
• The 5' portion of the gene was identical to the 1-8D gene product and the 3' was identical to the 9-27 gene product, but the existence of a transcript was not demonstrated by RT-PCR [26].
• Analysis at the single-cell level by indirect immunofluorescence revealed that mouse cells expressing 9-27 were less permissive for vesicular stomatitis virus than control cells not expressing 9-27 [4].
• The molecular weight was determined as 26,000-28,000 by gel filtration, 30,850 +/- 1500 by sedimentation analysis and 26,930-27,410 by calculation from the amino acid composition (Lys20-21, His3, Arg9, Asp21-22, Thr13, Ser18, Pro12-13, Glu23-24, Gly30, Ala16, Cys/29, Val19, Met1, Ile10, Leu13, Tyr14, Phe6, Trp3) [27].

References