An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation

McGarvey, Terence W.; Nguyen, Trang B.; Malkowicz, S. Bruce

doi:10.1002/jcb.20432

“…McGarvey et al [2005] have demonstrated that UBIAD1 (also known as TERE1) interacts with the carboxyl terminus of apoE. Secretion of apolipoprotein E (apoE) by brain glia has been suggested to require protein prenylation [Naidu et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

“…Studies examining protein localization will determine if mutant protein is located in the same membrane as wild-type and whether the clinical effects observed in SCCD patients are due to haploinsufficiency. Of specific interest will be examination of the published interaction between UBIAD1 and apolipoprotein E and whether SCCD mutations alter this interaction [McGarvey et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function

Weiss

¹

,

Kruth

²

,

Kuivaniemi

³

et al. 2008

American J of Med Genetics Pt A

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Schnyder crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease characterized by progressive corneal opacification resulting from abnormal deposition of cholesterol and phospholipids. Recently, six different mutations on the UBIAD1 gene on chromosome 1p36 were found to result in SCCD. The purpose of this article is to further characterize the mutation spectrum of SCCD and identify structural and functional consequences for UBIAD1 protein activity. DNA sequencing was performed on samples from 36 individuals from 14 SCCD families. One affected individual was African American and SCCD has not been previously reported in this ethnic group. We identified UBIAD1 mutations in all 14 families which had 30 affected and 6 unaffected individuals. Eight different UBIAD1 mutations, 5 novel (L121F, D118G, and S171P in exon 1, G186R and D236E in exon 2) were identified. In four families with DNA samples from both affected and unaffected individuals, the D118G, G186R, T175I, and G177R mutations cosegregated with SCCD. In combination with our previous report, we have identified the genetic mutation in UBIAD1 in 20 unrelated families with 10 (including 5 reported here), having the N102S mutation. The results suggest that N102S may be a mutation hot spot because the affected families were unrelated including Caucasian and Asian individuals. There was no genotype phenotype correlation except for the T175I mutation which demonstrated prominent diffuse corneal haze, typically without corneal crystals. Protein analysis revealed structural and functional implications of SCCD mutations which may affect UBIAD1 function, ligand binding and interaction with binding partners, like apo E.

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“…The pcDNA3.1HisC-TERE1 plasmid and the pTRE-REV-TERE1 retrovirus plasmids were previously described (McGarvey et al, 2001(McGarvey et al, , 2003(McGarvey et al, , 2005. The mammalian CMV expression plasmids pM12-NFLAG-TERE1 and pM12-NFLAG-TBL2 were obtained from GeneCopoeia.…”

Section: Expression Vectorsmentioning

confidence: 99%

“…TERE1's role in cholesterol metabolism, suggested by the APOE interaction (McGarvey et al, 2005), was reinforced by the association of point mutations in TERE1 with SCD, a corneal cholesterol and lipid accumulation disorder (Weiss et al, 2007). We transfected HEK293 cells with Flag-tagged wild-type and SCD mutant TERE1 plasmids with point mutations at N102S, D118G, L121F, S171P, T175I, G177R, N232S, D236E, and confirmed equivalent expression levels of the wild-type, mutant, and deletion proteins (Figs.…”

Section: Tere1 Scd Mutations Alter Cholesterol Levelsmentioning

confidence: 99%

“…TERE1 overexpression inhibited growth of transitional cell carcinoma cell lines J82 and HT1376, and prostate cancer cell lines PC3 and LnCaP (McGarvey et al, 2001(McGarvey et al, , 2003. A possible relationship between TERE1 and cellular lipids was recog-nized via the interaction of TERE1 with the APOE cholesterol carrier protein (McGarvey et al, 2005) and further supported by TERE1 mutations in Schnyder's corneal dystrophy (SCD), a rare disease of corneal cell cholesterol and lipid accumulation (Weiss et al, 2007;Nickerson et al, 2010). TERE1 expression has been reported to be mitochondrial and or in endoplasmic reticulum in different cell types (Nakagawa et al, 2010;Nickerson et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Bladder Tumor Suppressor Protein TERE1 (UBIAD1)Modulates Cell Cholesterol: Implications for Tumor Progression

Fredericks

¹

,

McGarvey

²

,

Wang

³

et al. 2011

DNA and Cell Biology

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Convergent evidence implicates the TERE1 protein in human bladder tumor progression and lipid metabolism. Previously, reduced TERE1 expression was found in invasive urologic cancers and inhibited cell growth upon re-expression. A role in lipid metabolism was suggested by TERE1 binding to APOE, a cholesterol carrier, and to TBL2, a candidate protein in triglyceride disorders. Natural TERE1 mutations associate with Schnyder's corneal dystrophy, characterized by lipid accumulation. TERE1 catalyzes menaquinone synthesis, known to affect cholesterol homeostasis. To explore this relationship, we altered TERE1 and TBL2 dosage via ectopic expression and interfering RNA and measured cholesterol by Amplex red. Protein interactions of wild-type and mutant TERE1 with GST-APOE were evaluated by binding assays and molecular modeling. We conducted a bladder tumor microarray TERE1 expression analysis and assayed tumorigenicity of J82 cells ectopically expressing TERE1. TERE1 expression was reduced in a third of invasive specimens. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibited nude mouse tumorigenesis. TERE1 and TBL2 proteins inversely modulated cellular cholesterol in HEK293 and bladder cancer cells from 20% to 50%. TERE1 point mutations affected APOE interactions, and resulted in cholesterol levels that differed from wild type. Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression.

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Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function

Weiss

¹

,

Kruth

²

,

Kuivaniemi

³

et al. 2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Schnyder crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease characterized by progressive corneal opacification resulting from abnormal deposition of cholesterol and phospholipids. Recently, six different mutations on the UBIAD1 gene on chromosome 1p36 were found to result in SCCD. The purpose of this article is to further characterize the mutation spectrum of SCCD and identify structural and functional consequences for UBIAD1 protein activity. DNA sequencing was performed on samples from 36 individuals from 14 SCCD families. One affected individual was African American and SCCD has not been previously reported in this ethnic group. We identified UBIAD1 mutations in all 14 families which had 30 affected and 6 unaffected individuals. Eight different UBIAD1 mutations, 5 novel (L121F, D118G, and S171P in exon 1, G186R and D236E in exon 2) were identified. In four families with DNA samples from both affected and unaffected individuals, the D118G, G186R, T175I, and G177R mutations cosegregated with SCCD. In combination with our previous report, we have identified the genetic mutation in UBIAD1 in 20 unrelated families with 10 (including 5 reported here), having the N102S mutation. The results suggest that N102S may be a mutation hot spot because the affected families were unrelated including Caucasian and Asian individuals. There was no genotype phenotype correlation except for the T175I mutation which demonstrated prominent diffuse corneal haze, typically without corneal crystals. Protein analysis revealed structural and functional implications of

show abstract

An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation

Cited by 34 publications

References 29 publications

Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function

Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function

The Bladder Tumor Suppressor Protein TERE1 (UBIAD1)Modulates Cell Cholesterol: Implications for Tumor Progression

Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function

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