Faculty Opinions recommendation of Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

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Drosophila Fragile X Protein, DFXR, Regulates Neuronal Morphology and Function in the Brain

Neuron ◽

10.1016/s0896-6273(02)00731-6 ◽

2002 ◽

Vol 34 (6) ◽

pp. 961-972 ◽

Cited By ~ 155

Author(s):

Joannella Morales ◽

P.Robin Hiesinger ◽

Andrew J. Schroeder ◽

Kazuhiko Kume ◽

Patrik Verstreken ◽

...

Keyword(s):

Fragile X ◽

Neuronal Morphology ◽

X Protein ◽

And Function ◽

The Brain

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Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice

Frontiers in Neuroscience ◽

10.3389/fnins.2021.749923 ◽

2021 ◽

Vol 15 ◽

Author(s):

Wenlu Pan ◽

Jing Pan ◽

Yan Zhao ◽

Hongzheng Zhang ◽

Jie Tang

Keyword(s):

Auditory Cortex ◽

Serotonin Transporter ◽

Cortical Neurons ◽

Pyramidal Neurons ◽

Frequency Tuning ◽

Primary Auditory Cortex ◽

Neuronal Morphology ◽

Neuronal Connections ◽

The Central Nervous System ◽

And Function

Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.

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Biogenesis and Function Mechanisms of Micro-RNAs and Their Role as Oncogenes and Tumor Suppressors

Systems Biology ◽

10.1007/978-4-431-87704-2_19 ◽

2009 ◽

pp. 183-189

Author(s):

Soken Tsuchiya ◽

Kazuya Terasawa ◽

Ryo Kunimoto ◽

Yasushi Okuno ◽

Fumiaki Sato ◽

...

Keyword(s):

Tumor Suppressors ◽

Micro Rnas ◽

And Function

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Rho GTPase Regulators and Effectors in Autism Spectrum Disorders: Animal Models and Insights for Therapeutics

Cells ◽

10.3390/cells9040835 ◽

2020 ◽

Vol 9 (4) ◽

pp. 835 ◽

Cited By ~ 1

Author(s):

Daji Guo ◽

Xiaoman Yang ◽

Lei Shi

Keyword(s):

Animal Models ◽

Rho Gtpases ◽

Rho Gtpase ◽

Autism Spectrum ◽

Neuronal Morphology ◽

Nucleotide Exchange ◽

Cellular Processes ◽

Research Initiative ◽

Genes Encoding ◽

And Function

The Rho family GTPases are small G proteins that act as molecular switches shuttling between active and inactive forms. Rho GTPases are regulated by two classes of regulatory proteins, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Rho GTPases transduce the upstream signals to downstream effectors, thus regulating diverse cellular processes, such as growth, migration, adhesion, and differentiation. In particular, Rho GTPases play essential roles in regulating neuronal morphology and function. Recent evidence suggests that dysfunction of Rho GTPase signaling contributes substantially to the pathogenesis of autism spectrum disorder (ASD). It has been found that 20 genes encoding Rho GTPase regulators and effectors are listed as ASD risk genes by Simons foundation autism research initiative (SFARI). This review summarizes the clinical evidence, protein structure, and protein expression pattern of these 20 genes. Moreover, ASD-related behavioral phenotypes in animal models of these genes are reviewed, and the therapeutic approaches that show successful treatment effects in these animal models are discussed.

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Novel Role for the Nuclear Phosphoprotein SET in Transcriptional Activation of P450c17 and Initiation of Neurosteroidogenesis

Molecular Endocrinology ◽

10.1210/mend.14.6.0469 ◽

2000 ◽

Vol 14 (6) ◽

pp. 875-888 ◽

Cited By ~ 38

Author(s):

Nathalie A. Compagnone ◽

Peilin Zhang ◽

Jean-Louis Vigne ◽

Synthia H. Mellon

Keyword(s):

Transcriptional Activation ◽

Neuronal Morphology ◽

Steroidogenic Factor 1 ◽

Mouse Fetus ◽

Neuronal Precursor Cells ◽

Endogenous Regulators ◽

Nuclear Phosphoprotein ◽

Inducible Protein ◽

And Function ◽

The Brain

Abstract Neurosteroids are important endogenous regulators of γ-aminobutryic acid (GABAA) and N-methyl-d-aspartate (NMDA) receptors and also influence neuronal morphology and function. Neurosteroids are produced in the brain using many of the same enzymes found in the adrenal and gonad. The crucial enzyme for the synthesis of DHEA (dehydroepiandrosterone) in the brain is cytochrome P450c17. The transcriptional strategy for the expression of P450c17 is clearly different in the brain from that in the adrenal or gonad. We previously characterized a novel transcriptional regulator from Leydig MA-10 cells, termed StF-IT-1, that binds at bases −447/−399 of the rat P450c17 promoter, along with the known transcription factors COUP-TF (chicken ovalbumin upstream promoter transcription factor), NGF-IB (nerve growth factor inducible protein B), and SF-1 (steroidogenic factor-1). We have now purified and sequenced this protein from immature porcine testes, identifying it as the nuclear phosphoprotein SET; a role for SET in transcription was not established previously. Binding of bacterially expressed human and rat SET to the DNA site at −418/−399 of the rat P450c17 gene transactivates P450c17 in neuronal and in testicular Leydig cells. We also found SET expressed in human NT2 neuronal precursor cells, implicating a role in neurosteroidogenesis. Immunocytochemistry and in situ hybridization in the mouse fetus show that the ontogeny and distribution of SET in the developing nervous system are consistent with SET being crucial for initiating P450c17 transcription. SET’s developmental pattern of expression suggests it may participate in the early ontogenesis of the nervous, as well as the skeletal and hematopoietic, systems. These studies delineate an important new factor in the transcriptional regulation of P450c17 and consequently, in the production of DHEA and sex steroids.

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