Your browser doesn't support javascript.
loading
Asparagine synthetase: Function, structure, and role in disease.
Lomelino, Carrie L; Andring, Jacob T; McKenna, Robert; Kilberg, Michael S.
Afiliação
  • Lomelino CL; Department of Biochemistry and Molecular Biology, Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610.
  • Andring JT; Department of Biochemistry and Molecular Biology, Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610.
  • McKenna R; Department of Biochemistry and Molecular Biology, Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610.
  • Kilberg MS; Department of Biochemistry and Molecular Biology, Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610. Electronic address: mkilberg@ufl.edu.
J Biol Chem ; 292(49): 19952-19958, 2017 12 08.
Article em En | MEDLINE | ID: mdl-29084849
Asparagine synthetase (ASNS) converts aspartate and glutamine to asparagine and glutamate in an ATP-dependent reaction. ASNS is present in most, if not all, mammalian organs, but varies widely in basal expression. Human ASNS activity is highly responsive to cellular stress, primarily by increased transcription from a single gene located on chromosome 7. Elevated ASNS protein expression is associated with resistance to asparaginase therapy in childhood acute lymphoblastic leukemia. There is evidence that ASNS expression levels may also be inversely correlated with asparaginase efficacy in certain solid tumors as well. Children with mutations in the ASNS gene exhibit developmental delays, intellectual disability, microcephaly, intractable seizures, and progressive brain atrophy. Thus far, 15 unique mutations in the ASNS gene have been clinically associated with asparagine synthetase deficiency (ASD). Molecular modeling using the Escherichia coli ASNS-B structure has revealed that most of the reported ASD substitutions are located near catalytic sites or within highly conserved regions of the protein. For some ASD patients, fibroblast cell culture studies have eliminated protein and mRNA synthesis or stability as the basis for decreased proliferation.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aspartato-Amônia Ligase / Regulação Enzimológica da Expressão Gênica / Mutação Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aspartato-Amônia Ligase / Regulação Enzimológica da Expressão Gênica / Mutação Limite: Animals / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article