细胞功能测定

Post-translational modification of p53 by ubiquitin resides in the center of a fine-tuned regulatory network that activates the tumor suppressor in response to genotoxic stress. Inhibition of p53 ubiquitination by DNA damage not only prevents p53 from degradation but also promotes i ...

Regulation of gene expression is essential for coordinated cell growth and development. The de-regulation of certain genes is also recognised to contribute to both heritable and acquired disease. Transcription factors influence the assembly and activity of transcription comp ...

ETS transcription factors are implicated in gene regulation during cell proliferation and in the development of the haematopoietic cell lineage. Characteristically, ETS proteins act in concert with other transcription factors and are regulated by post-translational modif ...

Transcription factors are usually unstable proteins. The degradation of the majority of transcription factors is through the ubiquitin proteasome pathway and is tightly regulated by E3 ubiquitin ligases. KLF5 is an important transcription factor regulating cell proliferati ...

Most transcription factors including nuclear receptors (NRs) act as sensors of the extracellular and intracellular compartments. As such, NRs serve as integrating platforms for a variety of stimuli and are targets for Post-translational modifications such as phosphorylation ...

The activity of transcription factors is often regulated by Post-translational modifications. A precondition for such modifications is the presence, in the corresponding mRNAs, of the exons that either directly encode the modifiable residues in question, or encode protein domai ...

Hypoxia-inducible factor-1 (HIF-1) has a central role in the mammalian program by which cells respond to hypoxia in both physiological and pathological situations. HIF-1 transcriptional activity, protein stabilization, protein–protein interaction, and cellular localiza ...

In this chapter, we review protocols for the analysis of nucleocytoplasmic shuttling of transcription factors and nuclear proteins, using two different approaches. The first involves the use of photoactivatable forms of the protein of interest by fusion to photoactivatable green f ...

Continuous nucleocytoplasmic shuttling of signal transducer and activator of transcription (STAT) proteins is a key to understand their function as cytokine-responsive transcription factors. STATs enter the nucleus both by carrier-dependent and carrier-independent t ...

In eukaryotes, regulation of signaling mediators/effectors in the nucleus is one of the principal mechanisms that govern duration and strength of signaling. Smads are a family of structurally related intracellular proteins that serve as signaling effectors for transforming gro ...

The proliferation-associated transcription factor FOXM1 is essential for cell cycle progression into mitosis. Using synchronized human fibroblasts we detected, by immunostaining, that FOXM1 is localized predominantly in the cytoplasm in cells at late-G1 and S phases. Nuclear t ...

The growth inhibition of dividing cells and most of the transcriptional responses upon TGF-β treatment depend on the Smad2, Smad3, and Smad4 transcription factors. These proteins shuttle continuously between the cytoplasm and the nucleus, transmitting the ligand status of the TGF-β re ...

Nuclear microenvironments are architecturally organized subnuclear sites where the regulatory machinery for gene expression, replication, and repair resides. This compartmentalization is necessary to attain required stoichiometry for organization and assembly of ...

Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily enter the brain and exert markedly diverse effects, such as the stress response of target neural cells. These effects are regulated via two receptor systems, the mineralocorticoid receptor (MR) and the ...

β-Catenin is a multifunctional protein which is overexpressed in several types of cancers. The subcellular location of β-catenin at the membrane junctions or in the nucleus determines its function in cell adhesion and transcription activation, respectively. The aberrant localiz ...

Post-translational modifications and subcellular localizations modulate transcription factors, generating a code that is deciphered into an activity. We describe our current understanding of these processes for Ets factors, which have recently been recognized for their im ...

Regulation of protein degradation is an important mechanism by which concentrations of proteins is controlled in cells. In addition to proteins involved in cell cycle regulation or mitosis, protein levels of many transcription factors are regulated by targeted proteosomal degrad ...

Human exposures to environmental toxicants have been associated with etiology of many diseases including inflammation, cancer, and cardiovascular and neurodegenerative disorders. To counteract the detrimental effect of environmental insults, mammalian cells have evo ...

Transcription factor proteins function in the nucleus to regulate gene expression. Many transcription factors are critical regulators of tumor progression. Conversely, many oncogenic and tumor suppressor proteins are transcription factors or other types of nuclear protei ...

The program PottersWheel has been developed to provide an intuitive and yet powerful framework for data-based modeling of dynamical systems like biochemical reaction networks. Its key functionality is multi-experiment fitting, where several experimental data sets from diffe ...