Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) catalyzes the rate-limiting step of ATP formation in eukaryotic cells. Here, we examined the post-transcriptional regulation of human beta-F1-ATPase mediated by the 3'-untranslated region of the mRNA (beta-3'-UTR). Biochemical analysis revealed that the adenosine/uridine (AU)-rich element-binding proteins TIA-1 (T-cell intracellular antigen-1), TIAR (TIA-1-related protein), and HuR (Hu antigen R) interact with the beta-F1-ATPase mRNA through an AU-rich sequence located to the 3'-UTR. Mouse embryonic fibroblasts (MEFs) knocked-out for TIA-1 or RNA interference (RNAi)-mediated knockdown of endogenous TIA-1, TIAR, or HuR in HeLa cells resulted in a decrease in beta-F1-ATPase protein expression. The expression of GFP from a chimeric reporter containing human beta-3'-UTR was also abolished in HeLa cells depleted of TIA-1, TIAR, or HuR. MEFs knocked-in for TIA-1 or the overexpression of RNAi-resistant TIA-1, TIAR, or HuR proteins in the RNAi-treated HeLa cells significantly restored the levels of the expression of both endogenous mouse beta-F1-ATPase protein or recombinant GFP.
 ...
PMID:Control of the ATP synthase beta subunit expression by RNA-binding proteins TIA-1, TIAR, and HuR. 1689 Jan 99

We have recently reported that RNA-binding proteins TIA-1 (T-cell intracellular antigen-1), TIAR (TIA-1 related protein), and HuR (Hu antigen R) modulate the expression of the ATP synthase beta-subunit mRNA (beta-F1-ATPase mRNA) [J.M. Izquierdo, Control of the ATP synthase beta subunit expression by RNA-binding proteins TIA-1, TIAR, and HuR, Biochem. Biophys. Res. Commun. 348 (2006) 703-711]. Here we found that PTB (Polypyrimidine Tract-Binding Protein) is a novel member of the ribonucleoprotein complex that interacts with the beta-F1-ATPase mRNA through an adenosine/uridine (AU)-rich element located to the beta-F1-ATPase 3'-untranslated region (beta-3'-UTR). Co-expression of GFP from a reporter mRNA quimera containing human beta-3'-UTR and recombinant PTB in HeLa cells increased the amount of GFP protein. Interestingly, this effect is not due to increased steady-state levels of GFP-beta-3'-UTR mRNA. Taken together, these results suggest that PTB regulates post-transcriptional expression of the beta-F1-ATPase mRNA at the translational level.
 ...
PMID:The RNA-binding protein PTB exerts translational control on 3'-untranslated region of the mRNA for the ATP synthase beta-subunit. 1746 48

Downregulation of the catalytic subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) is a hallmark of many types of cancer. The expression of beta-F1-ATPase is stringently controlled by posttranscriptional mechanisms. Herein, we pursue the identification of beta-F1-ATPase messenger RNA-binding proteins (beta-mRNABPs) that interact and could define the bioenergetic phenotype of the cancer cell in order to establish its relevance as markers of breast cancer progression. RNA immunoprecipitation and RNA affinity chromatography identify HuR as a beta-mRNABP that interacts with the 3'-untranslated region of the transcript. Subcellular fractionation and high-resolution immunoelectron microscopy revealed the cofractionation and presence of HuR in subcellular structures associated to liver mitochondria. Analysis of the expression level of HuR in a cohort of breast carcinomas shows its association with the degree of alteration of the bioenergetic phenotype of the tumor. Moreover, HuR expression is shown to be an independent marker of breast cancer prognosis. A low tumor expression of HuR predicts a higher risk of disease recurrence in early stage breast cancer patients as assessed by clinical and bioenergetic markers of prognosis, strongly supporting the incorporation of HuR as an additional marker for the follow-up of these patients. Mechanistically, overexpression experiments and short hairpin RNA-mediated silencing of HuR in human embryonic kidney and HeLa cells indicate that HuR is not regulating beta-F1-ATPase expression. Overall, the participation of additional RNA-binding proteins in controlling beta-F1-ATPase expression and therefore in defining the bioenergetic signature of the cancer cell is expected.
 ...
PMID:HuR and the bioenergetic signature of breast cancer: a low tumor expression of the RNA-binding protein predicts a higher risk of disease recurrence. 1868 67