Id |
Subject |
Object |
Predicate |
Lexical cue |
TextSentencer_T1 |
0-121 |
Sentence |
denotes |
Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit. |
TextSentencer_T2 |
122-283 |
Sentence |
denotes |
Congenital deficiencies of the human pyruvate dehydrogenase (PDH) complex are considered to be due to loss of function mutations in one of the component enzymes. |
TextSentencer_T3 |
284-377 |
Sentence |
denotes |
Here we describe a case of PDH deficiency associated with the PDH E1beta subunit (PDHB) gene. |
TextSentencer_T4 |
378-469 |
Sentence |
denotes |
The clinical phenotype of the patient was consistent with reported cases of PDH deficiency. |
TextSentencer_T5 |
470-630 |
Sentence |
denotes |
Cultured skin fibroblasts demonstrated a 55% reduction in PDH activity and markedly decreased immunoreactivity for PDHB protein, compared with healthy controls. |
TextSentencer_T6 |
631-782 |
Sentence |
denotes |
Surprisingly, nucleotide sequence analyses of cDNAs corresponding to the patient PDH E1alpha (PDHA1) and PDHB genes revealed no pathological mutations. |
TextSentencer_T7 |
783-912 |
Sentence |
denotes |
Moreover, the relative expression level of PDHB mRNA and the rates of transcription and translation of the PDHB gene were normal. |
TextSentencer_T8 |
913-1114 |
Sentence |
denotes |
However, PDC activity could be restored in cells from this patient following treatment with MG132, a specific proteasome inhibitor, and normal levels of E1beta could be detected in MG132-treated cells. |
TextSentencer_T9 |
1115-1408 |
Sentence |
denotes |
Similar results were obtained following treatment with Tyr-phostin 23 (Tyr23), a specific inhibitor of epidermal growth factor receptor-protein-tyrosine kinase (EGFR-PTK), which also restored E1beta protein levels to those in cells from healthy subjects or from patients with PDHA1 deficiency. |
TextSentencer_T10 |
1409-1684 |
Sentence |
denotes |
The index patient's cells contained a high basal level of EGFR-PTK activity that correlated with the high level of ubiquitination of cellular proteins, although the total EGFR protein levels were similar to those in cells from Elalpha-deficient subjects and healthy subjects. |
TextSentencer_T11 |
1685-1934 |
Sentence |
denotes |
These data indicate that PDH deficiency in our patient involves a post-translational modification in which EGFR-PTK-mediated tyrosine phosphorylation of the E1beta protein leads to enhanced ubiquitination followed by proteasome-mediated degradation. |
TextSentencer_T12 |
1935-2073 |
Sentence |
denotes |
They also provide a novel mechanism accounting for congenital deficiency of the PDH complex and perhaps other inborn errors of metabolism. |
T1 |
0-121 |
Sentence |
denotes |
Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit. |
T2 |
122-283 |
Sentence |
denotes |
Congenital deficiencies of the human pyruvate dehydrogenase (PDH) complex are considered to be due to loss of function mutations in one of the component enzymes. |
T3 |
284-377 |
Sentence |
denotes |
Here we describe a case of PDH deficiency associated with the PDH E1beta subunit (PDHB) gene. |
T4 |
378-469 |
Sentence |
denotes |
The clinical phenotype of the patient was consistent with reported cases of PDH deficiency. |
T5 |
470-630 |
Sentence |
denotes |
Cultured skin fibroblasts demonstrated a 55% reduction in PDH activity and markedly decreased immunoreactivity for PDHB protein, compared with healthy controls. |
T6 |
631-782 |
Sentence |
denotes |
Surprisingly, nucleotide sequence analyses of cDNAs corresponding to the patient PDH E1alpha (PDHA1) and PDHB genes revealed no pathological mutations. |
T7 |
783-912 |
Sentence |
denotes |
Moreover, the relative expression level of PDHB mRNA and the rates of transcription and translation of the PDHB gene were normal. |
T8 |
913-1114 |
Sentence |
denotes |
However, PDC activity could be restored in cells from this patient following treatment with MG132, a specific proteasome inhibitor, and normal levels of E1beta could be detected in MG132-treated cells. |
T9 |
1115-1408 |
Sentence |
denotes |
Similar results were obtained following treatment with Tyr-phostin 23 (Tyr23), a specific inhibitor of epidermal growth factor receptor-protein-tyrosine kinase (EGFR-PTK), which also restored E1beta protein levels to those in cells from healthy subjects or from patients with PDHA1 deficiency. |
T10 |
1409-1684 |
Sentence |
denotes |
The index patient's cells contained a high basal level of EGFR-PTK activity that correlated with the high level of ubiquitination of cellular proteins, although the total EGFR protein levels were similar to those in cells from Elalpha-deficient subjects and healthy subjects. |
T11 |
1685-1934 |
Sentence |
denotes |
These data indicate that PDH deficiency in our patient involves a post-translational modification in which EGFR-PTK-mediated tyrosine phosphorylation of the E1beta protein leads to enhanced ubiquitination followed by proteasome-mediated degradation. |
T12 |
1935-2073 |
Sentence |
denotes |
They also provide a novel mechanism accounting for congenital deficiency of the PDH complex and perhaps other inborn errors of metabolism. |