The term "functional redundancy" has been used as key words in foreign literature recently. However, it is rarely appeared in Chinese literature. Functional redundancy is an important characteristic of cytokines and transcription factors. The author gives personal opinion on this term for discussion.
Animals ; Cytokines ; physiology ; Humans ; Transcription Factors ; physiology

Blood Vessels ; physiology ; Humans ; Kruppel-Like Transcription Factors ; metabolism ; physiology

Hedgehog (Hh) signaling pathway plays an important role during embryonic development and pattern formation. Disruption of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its downstream members, the so-called "canonical signaling pathway". Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a "signaling center" during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as "non-canonical signaling pathways", which can be subdivided into two modules: (i) those not requiring Smo and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways.
Animals ; Cilia ; physiology ; Hedgehog Proteins ; physiology ; Receptors, G-Protein-Coupled ; physiology ; Signal Transduction ; Transcription Factors ; physiology

Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.
Animals ; Energy Metabolism ; physiology ; Humans ; Transcription Factors ; metabolism

The cAMP-responsive element binding protein (CREB)-regulated transcription coactivator, CRTC (also known as transducer of regulated CREB, TORC), is identified as a potent modulator of cAMP response element (CRE)-driven gene transcription. The CRTC family consists of three members (CRTC1-3), among which the CRTC1 shows the highest expression in the brain. Several studies have demonstrated that the CRTC1 plays critical roles in neuronal dendritic growth, long-term synaptic plasticity, memory consolidation and reconsolidation etc., whereas dysfunction of CRTC1 is mainly involved in neurodegenerative disorders. In light of these findings, we aim to review recent research reports that indicate the CRTC1 dysfunction and its underlying mechanisms in the neurodegenerative disorders.
Brain ; physiology ; Dendrites ; physiology ; Humans ; Neurodegenerative Diseases ; physiopathology ; Neuronal Plasticity ; Transcription Factors ; physiology

Animals ; Cell Differentiation ; physiology ; Cell Proliferation ; Hepatocytes ; transplantation ; Humans ; Transcription Factors ; genetics ; Transcription, Genetic

Biomedical Research ; trends ; Female ; Genital Neoplasms, Female ; Humans ; Nuclear Proteins ; physiology ; Transcription Factors ; physiology

More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings. At the post-translational level, it is regulated through the ubiquitin-proteasome pathway. In vitro and in vivo studies have revealed that manipulation of these signaling pathways not only controls development, but also leads to the regeneration of cochlear hair cells after damage. Recent progress toward understanding the signaling networks involved in hair cell development and regeneration has led to the development of new strategies to replace lost hair cells. This review focuses on our current understanding of the signaling pathways that regulate Atoh1 in the cochlea.
Basic Helix-Loop-Helix Transcription Factors/physiology* ; Cell Differentiation ; Cochlea/physiology* ; Hair Cells, Auditory/physiology* ; Hearing Loss/etiology* ; Humans ; Proteasome Endopeptidase Complex/physiology* ; Signal Transduction/physiology* ; Transcription Factors/physiology* ; Ubiquitin/metabolism* ; Wnt Signaling Pathway ; beta Catenin/physiology*

The sleep-wake cycle displays a characteristic 24-hour periodicity, providing an opportunity to dissect the endogenous circadian clock through the study of aberrant behaviour. This article surveys the properties of circadian clocks, with emphasis on mammals. Information was obtained from searches of peer-reviewed literature in the PUBMED database. Features that are highlighted include the known molecular components of clocks, their entrainment by external time cues and the output pathways used by clocks to regulate metabolism and behaviour. A review of human circadian rhythm sleep disorders follows, including recent discoveries of their genetic basis. The article concludes with a discussion of future approaches to the study of human circadian biology and sleep-wake behaviour.
ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; physiology ; CLOCK Proteins ; Circadian Rhythm ; genetics ; physiology ; Humans ; Neurons, Afferent ; physiology ; Neurons, Efferent ; physiology ; Polymorphism, Single Nucleotide ; Sleep Disorders, Circadian Rhythm ; genetics ; physiopathology ; Suprachiasmatic Nucleus ; cytology ; physiology ; Trans-Activators ; physiology

Cholestatic liver diseases are characterized by impairments of bile flows and accumulations of biliary constituents such as bile acids and bilirubin. The changes of phase I and II metabolism and the hepatobiliary transport system minimize cholestatic liver injury. These adaptive responses are transcriptionally regulated by several nuclear receptors. Recent studies have revealed that the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are key nuclear receptors for regulating many of the adaptive responses noted in cholestasis. PXR and CAR coordinately regulate not only bile acid metabolism and transport, but also bilirubin clearance. PXR and CAR ligands may be useful in the future for the treatment of cholestatic liver disease.
Transcription Factors/metabolism/*physiology ; Receptors, Steroid/metabolism/*physiology ; Receptors, Cytoplasmic and Nuclear/metabolism/*physiology ; Humans ; Cholestasis/metabolism/*physiopathology