Mutations in the<i>UBIAD1</i>Gene on Chromosome Short Arm 1, Region 36, Cause Schnyder Crystalline Corneal Dystrophy

Weiss, Jayne S.; Kruth, Howard S.; Kuivaniemi, Helena; Tromp, Gerard; White, Peter S.; Winters, Robert W.; Lisch, Walter; Henn, Wolfram; Denninger, Elke; Krause, Matthias; Wasson, Paul J.; Ebenezer, Neil D.; Mahurkar, Sunil; Nickerson, Michael L.

doi:10.1167/iovs.07-0845

Cited by 96 publications

(107 citation statements)

References 31 publications

(43 reference statements)

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“…The heme regulatory motif (30-XCPXX-34) and oxidoreductase motif (145-CXXC-148) suggest that TERE1 activity may be affected by cellular redox state (Weiss et al, 2007). The approximate polyclonal antibody binding sites and engineered stop mutations at Y174 and E242 used in this study and the prominent loops 1-3 that contain mutations (in red) associated with SCD are also shown (Weiss et al, 2007;Nickerson et al, 2010). These loops may constitute a binding interface for interacting proteins, APOE and TBL2.…”

Section: Features Of Tere1 Proteinmentioning

confidence: 60%

Section: Features Of Tere1 Proteinmentioning

confidence: 99%

“…The adjacent aspartate-rich, FARM motif, DDXXXXD, from 117-DDRTLVD-123 is similar to farnesyl diphosphate synthetase (Szkopinska and Plochocka, 2005) and has been referred to as a putative ligand/polyprenyldiphosphate binding site (Weiss et al, 2007). The heme regulatory motif (30-XCPXX-34) and oxidoreductase motif (145-CXXC-148) suggest that TERE1 activity may be affected by cellular redox state (Weiss et al, 2007). The approximate polyclonal antibody binding sites and engineered stop mutations at Y174 and E242 used in this study and the prominent loops 1-3 that contain mutations (in red) associated with SCD are also shown (Weiss et al, 2007;Nickerson et al, 2010).…”

Section: Features Of Tere1 Proteinmentioning

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%

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

Fredericks

McGarvey

Wang

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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Section: Features Of Tere1 Proteinmentioning

confidence: 60%

Section: Features Of Tere1 Proteinmentioning

confidence: 99%

Section: Features Of Tere1 Proteinmentioning

confidence: 99%

Section: Tere1 Scd Mutations Alter Cholesterol Levelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Fredericks

McGarvey

Wang

et al. 2011

DNA and Cell Biology

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

Weiss

Kruth

Kuivaniemi

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

Weiss

Kruth

Kuivaniemi

et al. 2008

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

show abstract

Mutations in theUBIAD1Gene on Chromosome Short Arm 1, Region 36, Cause Schnyder Crystalline Corneal Dystrophy

Cited by 96 publications

References 31 publications

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

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

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

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