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Last update 23 Jan 2025

BRSK

Last update 23 Jan 2025

Basic Info

Synonyms

Brain selective kinases, Brain-specific kinases, SAD kinases

Introduction-

Drugs associated with BRSK

GW296115

Target

BRSK2

Mechanism

BRSK2 inhibitors

Active Org.

The University of North Carolina at Chapel Hill

Originator Org.

The University of North Carolina at Chapel Hill

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BRSK

100 Translational Medicine associated with BRSK

0 Patents (Medical) associated with BRSK

211

Literatures (Medical) associated with BRSK

01 Jan 2025·Bioresource Technology

Identification of xenobiotic response element family transcription regulator SadR from sulfonamides-degrading strain Microbacterium sp. HA-8 and construction of biosensor to detect sulfonamides

Article

Author: Liu, Hongfei ; Hong, Qing ; Pan, Kaihua ; Wang, Fang ; Hu, Junqiang ; Li, Qian ; Huang, Yanni ; Zhu, Qian ; Zhu, Weihao ; Wang, Changchang ; Jiang, Mingli ; Zhang, Mingliang

Deciphering the regulatory mechanisms of sulfonamides (SAs) metabolism will contribute to a deeper understanding of SAs degradation in the environment. In this study, a SAs-degrading strain Microbacterium sp. HA-8 harboring a highly conserved SAs-degrading genes sadABC was isolated. SadR was a newly discovered regulator, belonging to xenobiotic response element (XRE) family, which negatively regulated the transcription of sadAB genes. Specifically, SadR bound to the sadA promoter region to repress the expression of sadAB genes. While, SAs prevented SadR from binding to sadA promoter to induce the expression of sadAB genes. Then, a whole-cell biosensor, Escherichia coli DH5α/pSRmCherry was constructed to detect SAs. The dose-dependent fluorescence of the biosensor exhibited a good fit to Hill equation. In summary, this study revealed the regulatory mechanism of SAs degradation in strain HA-8 and developed an innovative biosensor technique for detecting SAs, holding promise for future applications in environmental monitoring.

01 Sep 2024·Translational Cancer Research

Article

BackgroundHepatocellular carcinoma (HCC) remains one of the most common human cancers, the death cases induced by HCC are increasing these years. Endoplasmic reticulum stress (ERS) occurs when misfolded proteins cannot be disposed of properly. It is reported that ERS plays a crucial role in the pathogenesis of human malignant tumors. The aim of this study is to construct a novel gene signature based on ERS for predicting prognosis in HCC.MethodsThe data of HCC patients were downloaded from public databases. The Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to construct ERS-related gene signature. The cases were divided into high- and low-risk groups based on the ERS-related gene signature in The Cancer Genome Atlas (TCGA) cohort. Subsequently, the differences in messenger ribonucleic acid (mRNA) expression patterns, immune status, tumor mutation burden (TMB) and copy number variants (CNV) were investigated between high- and low-risk groups. Then, a predictive nomogram according to the ERS-related gene signature and clinicopathological variables was established. At last, we explored the biological functions of TMX1 which had the biggest coefficient and we investigated the effect of BRSK2 on apoptosis in HCC.ResultsIn our study, a 9-gene ERS-related gene signature was constructed. The results showed that patients in the low-risk group had a better prognosis than the high-risk group patients. The results of receiver operating characteristic (ROC) curves revealed that the area under the curve (AUC) was 0.784 at 1 year, 0.780 at 2 years, 0.793 at 3 years in the training set. While in validation cohort, this index was 0.694 at 1 year, 0.622 at 2 years, 0.613 at 3 years respectively. The analysis of immune status revealed an immunosuppressive microenvironment in the high-risk group. The analysis of TMB and CNV revealed that the high-risk group patients had a higher genomic mutation frequency. In Univariate Cox regression analysis, the hazard ratio of RiskScore was 2.718 [95% confidence interval (CI): 2.173-3.399]. In Multivariate Cox regression analysis, the hazard ratio of RiskScore was 2.422 (95% CI: 1.805-3.25). Then, we established a nomogram according to the RiskScore and Eastern Cooperative Oncology Group performance status. The AUCs of the nomogram were 0.851 at 1 year, 0.860 at 2 years, and 0.866 at 3 years. At last, we found that TMX1 knockdown can inhibit the proliferation and migration of Huh7 and HepG2 cells. In addition, BRSK2 knockdown could promote the apoptosis induced by ERS.ConclusionsIn our study, a novel ERS-related gene signature was constructed to predict the prognosis of HCC patients. In addition, TMX1 and BRSK2 could promote the progression of HCC. This study may provide a new understanding for HCC.

01 Sep 2024·Tuberculosis

M. tuberculosis PrrA binds the dosR promoter and regulates mycobacterial adaptation to hypoxia

Article

Author: Wan, Zijian ; Wang, Shaopeng ; Jiang, Jiapei ; Childress, Alexia ; Haller, Yannik A ; Haydel, Shelley E

The PrrAB two-component system (TCS) is essential for Mycobacterium tuberculosis viability. Previously, it was demonstrated that PrrA binds DNA in the absence of PrrB-mediated transphosphorylation and that non-cognate serine/threonine-kinases phosphorylate PrrA threonine-6 (T6). Therefore, we investigated the differential binding affinity and regulatory properties of the M. tuberculosis-derived wild-type PrrA, PrrA phosphomimetic (D58E, T6E), and PrrA phosphoablative (D58A, T6A) proteins with the prrA^Mtb, dosR^Mtb, and cydA^Mtb genes. While we hypothesized greater DNA binding affinity and more pronounced regulation by PrrA phosphomimetic variants, recombinant, wild-type PrrA^Mtb bound DNA with greatest affinity. Collectively, wild-type PrrA^Mtb recombinant protein displayed the highest binding affinity to the dosR^Mtb promoter (K_D 3.46 ± 2.09 nM), followed by the prrA^Mtb promoter (K_D 9.00 ± 2.66 nM). To establish PrrA^Mtb regulatory activity, we constructed M. smegmatis ΔprrAB^Msmeg::prrA^Mtb strains with each of the PrrA^Mtb variants and extrachromosomal prrA^Mtb, dosR^Mtb, and cydA^Mtb promoter-mCherry reporter fusions. Our findings showed that PrrA^Mtb is autoregulatory and induces dosR^Mtb expression only during in vitro, hypoxic growth. Combined expression of prrAB^Mtb in M. smegmatis ΔprrAB significantly induced cydA^Mtb promoter-mCherry expression. Our studies advanced the understanding of PrrA function and PrrAB phosphorylation-mediated regulatory mechanisms and control of mycobacterial dosR and cydA hypoxic and low-oxygen responsive genes.

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