Biology subjects

Shang, Q.

Publications and source records attributed to Shang, Q..

6 recordsLinked to original sources

bioRxiv2024

Multiple allostery in the regulation of PDGFR beta kinase activities

Platelet-derived growth factor receptor beta (PDGFR{beta}), a type III receptor tyrosine kinase (RTK) with a featured kinase insert, regulates important cellular functions. Dysregulation of PDGFR{beta} is associated with cardiovascular and fibrosis diseases. Thus, its kinase activity needs to be precisely regulated under physiological conditions. Early studies demonstrated that its kinase was autoinhibited by its juxtamembrane segment and activated by transphosphorylation. However, additional mechanisms are required for the comprehensive regulation of the receptor kinase. Herein, we provide evidences that dimerization of activated kinases, autoinhibition by the kinase insert, and dimerization of inactive kinase, all contribute to the regulation of the receptor kinase. Moreover, we find such multiple allosteric regulation is also conserved in other type III RTKs, including colony stimulating factor 1 receptor (CSF1R). Impairing the allosteric regulation of CSF1R is associated with malfunctions of microglia and demyelination of neurons in Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS).

biophysics↗

bioRxiv2023

GABRD promotes the progression of breast cancer through CDK1-dependent cell cycle regulation

PurposeY-aminobutyric acid (GABA) is an important inhibitory amino acid neurotransmitter that exerts its biological function by binding to GABA receptors, which not only play an important role in neuromodulation, but also involved in regulating the development of tumors. Gamma-aminobutyric acid type A receptor subunit delta (GABRD) encodes the {delta} subunit of GABAA receptor, its impact on breast cancer has not been clearly studied. This study is aiming to reveal the relationship between GABRD and breast cancer development. MethodsWe performed a tissue microarray to quantify GABRD expression levels in tumor tissue and paracarcinoma tissue. The regulation of GABRD in the proliferation, migration, and apoptosis of breast cancer was examined by a loss-of-function study. A GeneChip microarray was used to probe GABRD for potential downstream molecules. The interaction between GABRD and CDK1 was verified by a set of functional tests and rescue experiments as well as coimmunoprecipitation. ResultsGABRD was expressed at significantly higher levels in tumor tissues and was associated with advanced tumor progression. Silencing GABRD resulted in a significant decrease in proliferation and migration and an increase in apoptosis of breast cancer. GABRD regulated the cell cycle by directly interacting with CDK1, which was identified as an important downstream target. ConclusionGABRD is the breast cancer-related gene and highlights the importance of the GABRD-CDK1 axis in regulating breast cancer proliferation, which provides potential for the development of novel therapeutics.

cancer biology↗

bioRxiv2022

Ancestral Body Plan and Adaptive Radiation of Sauropterygian Marine Reptiles

Mesozoic was the age of reptiles that not only occupied the land and sky but also adapted to the sea. Sauropterygia, from turtle-like placodonts, lizard-like pachypleurosaurs, and predatory nothosaurs to long-necked pistosaurs including plesiosaurs, is one of the most predominant lineages among secondarily aquatic reptiles. However, we know little about the early evolution of sauropterygians involving the morphological gaps among aforementioned sub-groups and their ancestral body-plan, because the Early Triassic fossil remains are scarce shortly after their origin. Here we report a skeleton from the Early Triassic in South China, representing the oldest known complete specimen related to Sauropterygia. It can be referred to Hanosaurus hupehensis and shows a mosaic morphology combining the characters of multiple sauropterygian sub-lineages. We constructed an updated character matrix obtaining the hitherto most comprehensive phylogeny of Triassic sauropterygians, and Hanosaurus hupehensis is stably resolved as the basal-most member of the Sauropterygiformes (clade nov.). Sauropterygians were previously considered using limb propulsion for the movement that is distinguishable from ichthyosaurs and other marine reptiles, but this skeleton reflects an ancestral body plan of sauropterygians unexpectedly developing an elongate trunk and four short limbs, being different from most sauropterygians but more convergently similar to the basal members of other marine reptilian lineages in body shape. After this convergence, we confirm the rapid adaptive radiation of sauropterygiform reptiles following the end-Permian mass extinction. Our results provide an evolutionary framework of sauropterygian marine reptiles and highlight the integrations of both convergences and divergences when an emerging animal lineage arises.

paleontology↗

bioRxiv2021

Breast tumor IGF-1R regulates cell adhesion and metastasis: Alignment of mouse single cell and human breast cancer transcriptomics

The acquisition of a metastatic phenotype is the critical event that determines patient survival from breast cancer. Several receptor tyrosine kinases have functions both in promoting and inhibiting metastasis in breast tumors. Although the insulin-like growth factor 1 receptor (IGF-1R) has been considered a target for inhibition in breast cancer, low levels of IGF-1R expression are associated with worse overall patient survival. To determine how reduced IGF-1R impacts tumor phenotype, we used weighted gene correlation network analysis (WGCNA) of METABRIC patient data and identified gene modules specific to cell cycle, adhesion, and immune cell signaling inversely correlated with IGF-1R expression in human breast cancers. Integration of human patient data with data from mouse tumors revealed similar pathways necessary for promoting metastasis in basal-like tumors with reduced signaling or expression of the IGF-1R. Functional analyses revealed the basis for the enhanced metastatic phenotype including alterations in E- and P-cadherins.

cancer biology↗

bioRxiv2020

Physiological and pathological changes in the enteric nervous system of rotenone-exposed mice as potential early biomarkers for Parkinson's disease

Parkinsons disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. We have shown that environmental toxins can trigger the disease by acting on the ENS and on the autonomic nervous system. Oral exposure to the pesticide rotenone, a mitochondrial Complex I inhibitor, leads to decreased stool depositions in mice. Here we analyzed the effect of rotenone on the function and structure of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations makes them ideal candidates to be used as biomarkers for the detection of Parkinsons disease in its early stages.

neuroscience↗

bioRxiv2020

Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

immunology↗