MondoA senses adenine nucleotides: transcriptional induction of thioredoxin-interacting protein.

The MondoA-Mlx transcription complex plays a pivotal role in glucose homoeostasis by activating target gene expression in response to G6P (glucose 6-phosphate), the first reaction intermediate in glycolysis. TXNIP (thioredoxin-interacting protein) is a direct and glucose-responsive target of MondoA that triggers a negative-feedback loop by restricting glucose uptake when G6P levels increase. We show in the present study that TXNIP expression is also activated by AICAR (5-amino-4-imidazolecarboxamide ribofuranoside) and adenosine.

Glucose controls nuclear accumulation, promoter binding, and transcriptional activity of the MondoA-Mlx heterodimer.

Maintenance of energy homeostasis is a fundamental requirement for organismal fitness: defective glucose homeostasis underlies numerous metabolic diseases and cancer. At the cellular level, the ability to sense and adapt to changes in intracellular glucose levels is an essential component of this strategy. The basic helix-loop-helix-leucine zipper (bHLHZip) transcription factor complex MondoA-Mlx plays a central role in the transcriptional response to intracellular glucose concentration.

Protein solubility and folding enhancement by interaction with RNA.

While basic mechanisms of several major molecular chaperones are well understood, this machinery has been known to be involved in folding of only limited number of proteins inside the cells. Here, we report a chaperone type of protein folding facilitated by interaction with RNA. When an RNA-binding module is placed at the N-terminus of aggregation-prone target proteins, this module, upon binding with RNA, further promotes the solubility of passenger proteins, potentially leading to enhancement of proper protein folding.

Assessment of substrate-stabilizing factors for DnaK on the folding of aggregation-prone proteins.

Hydrophobic interactions between molecular chaperones and their nonnative substrates have been believed to be mainly responsible for both substrate recognition and stabilization against aggregation. However, the hydrophobic contact area between DnaK and its substrate proteins is very limited and other factors of DnaK for the substrate stabilization could not be excluded. Here, we covalently fused DnaK to the N-termini of aggregation-prone proteins in vivo.

N-terminal domains of native multidomain proteins have the potential to assist de novo folding of their downstream domains in vivo by acting as solubility enhancers.

The fusion of soluble partner to the N terminus of aggregation-prone polypeptide has been popularly used to overcome the formation of inclusion bodies in the E. coli cytosol. The chaperone-like functions of the upstream fusion partner in the artificial multidomain proteins could occur in de novo folding of native multidomain proteins.

N-Glycosylation of secretion enhancer peptide as influencing factor for the secretion of target proteins from Saccharomyces cerevisiae.

hIL-1beta-derived polypeptide, when fused to the N-terminal end of target proteins, exerts a potent secretion enhancer function in Saccharomyces cerevisiae. We investigated the effect of N-glycosylation of the secretion enhancer peptide on the secretion of target proteins. The N-terminal 24 amino acids (Ser5-Ala28) of human interleukin 1beta (hIL-1beta) and interleukin 1 receptor antagonist (IL-1ra) were used as secretion enhancer for synthesizing recombinant human granulocyte-colony stimulating factor (rhG-CSF) from S.