GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:10749989

From GONUTS
Jump to: navigation, search
Citation

El Ghouzzi, V, Legeai-Mallet, L, Aresta, S, Benoist, C, Munnich, A, de Gunzburg, J and Bonaventure, J (2000) Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location. Hum. Mol. Genet. 9:813-9

Abstract

H-TWIST belongs to the family of basic helix-loop-helix (bHLH) transcription factors known to exert their activity through dimer formation. We have demonstrated recently that mutations in H-TWIST account for Saethre-Chotzen syndrome (SCS), an autosomal dominant craniosynostosis syndrome characterized by premature fusion of coronal sutures and limb abnormalities of variable severity. Although insertions, deletions, nonsense and missense mutations have been identified, no genotype-phenotype correlation could be found, suggesting that the gene alterations lead to a loss of protein function irrespective of the mutation. To assess this hypothesis, we studied stability, dimerization capacities and subcellular distribution of three types of TWIST mutant. Here, we show that: (i) nonsense mutations resulted in truncated protein instability; (ii) missense mutations involving the helical domains led to a complete loss of H-TWIST heterodimerization with the E12 bHLH protein in the two-hybrid system and dramatically altered the ability of the TWIST protein to localize in the nucleus of COS-transfected cells; and (iii) in-frame insertion or missense mutations within the loop significantly altered dimer formation but not the nuclear location of the protein. We conclude that at least two distinct mechanisms account for loss of TWIST protein function in SCS patients, namely protein degradation and subcellular mislocalization.

Links

PubMed

Keywords

Animals; COS Cells; Cell Nucleus/metabolism; Craniosynostoses/genetics; Genotype; Hydrolysis; Mutation; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phenotype; Transcription Factors; Twist Transcription Factor; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYOD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15672

F

Seeded From UniProt

complete

HUMAN:MYOD1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MYOD1

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15672

F

Seeded From UniProt

complete

HUMAN:TWST1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15923-1

F

Seeded From UniProt

complete

HUMAN:TWST1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TFE2

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15672

F

Seeded From UniProt

complete

HUMAN:TFE2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TWST1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TWST1

enables

GO:0043425: bHLH transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15923-1

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.