IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-08

Doyeong Kim, Sang-Min Park, Seo-Young Lee, Jinchul Kim, Han-Byul Jung, Young Sook Kim, Sun-Ku Chung

{"title":"Antisense-mediated splicing correction as a therapeutic approach for p53 K120R mutation.","authors":"Doyeong Kim, Sang-Min Park, Seo-Young Lee, Jinchul Kim, Han-Byul Jung, Young Sook Kim, Sun-Ku Chung","doi":"","DOIUrl":"","url":null,"abstract":"The TP53 c.359A＞G mutation significantly disrupts the expression of the major TP53 transcript variant encoding p53 K120R by generating a new splice donor site. An antisense morpholino oligomer (AMO) targeting this mutation successfully restored normal splicing and the expression of the major TP53 variant. Given that p53 exerts its tumor suppressor function by regulating target genes responsible for growth arrest or apoptosis, the p53 K120R protein enhanced by AMO exhibits impaired transcriptional regulation of CDKN1A, a key growth arrest gene, while maintaining normal induction of the pro-apoptotic BBC3 gene. As a result, the mutant p53 K120R protein shows a defective cell growth arrest phenotype but retains apoptotic function, suggesting that it may still possess some tumor suppressor activity. Furthermore, lysine 120, known to provide a critical acetylation site for p53 activation, highlights the relevance of acetylation in tumor suppression through studies of the p53 K120R mutant. However, our findings demonstrate that targeting mutant TP53 mRNA with AMO is essential for restoring p53 function. In conclusion, this study emphasizes the potential of AMO-mediated splice correction as a therapeutic approach for TP53 mutations.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins. N 端和 C 端 LIR 基团在 RavZ 和 ATG4B 蛋白的催化活性和膜靶向性中的不同作用。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-08

Sang-Won Park, Ju-Hui Park, Haneul Choi, Pureum Jeon, Seung-Hwan Lee, Won-Dong Shin, Hun-Joo Kim, Jin-A Lee, Deok-Jin Jang

{"title":"Differential roles of N- and C-terminal LIR motifs in the catalytic activity and membrane targeting of RavZ and ATG4B proteins.","authors":"Sang-Won Park, Ju-Hui Park, Haneul Choi, Pureum Jeon, Seung-Hwan Lee, Won-Dong Shin, Hun-Joo Kim, Jin-A Lee, Deok-Jin Jang","doi":"","DOIUrl":"","url":null,"abstract":"Mammalian ATG8 proteins (mATG8s) are essential for selective autophagy because they recruit various proteins with LC3- interacting region (LIR) motifs to autophagic membranes. The RavZ protein, secreted by Legionella pneumophila, and mammalian ATG4B possess functional LIR motifs that participate in lipidated mATG8 deconjugation on autophagic membranes. RavZ comprises three functional LIR motifs at the N- and Cterminal sides of its catalytic domain (CAD). This study demonstrated that LIR motifs at the N-terminal side of the CAD of RavZ are involved in autophagic membrane targeting and substrate recognition, while LIR motif at the C-terminal side facilitate autophagic membrane targeting. Our results also revealed that the C-terminal LIR motif in human ATG4B is pivotal in delipidating LC3B-phosphatidylethanolamine (PE), but it plays a minor role in pro-LC3B priming in the cytosol. Therefore, introducing a functional LIR motif to the N-terminal of ATG4B does not affect LC3B-PE delipidation. This study clearly described the position-dependent roles of LIR motifs in RavZ and ATG4B in cellular contexts.","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Specialized pro-resolving mediator 7S MaR1 inhibits IL-6 expression via modulating ROS/p38/ERK/NF-κB pathways in PM₁₀-exposed keratinocytes. 通过调节 PM10 暴露角质细胞中的 ROS/p38/ERK/NF-κB 通路，特化的促溶解介质 7S MaR1 可抑制 IL-6 的表达。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-08

Jinju Kim, Hyo-Min Park, Chae-Min Lim, Kyeong-Bae Jeon, Seonhwa Kim, Jin Lee, Jin-Tae Hong, Deok-Kun Oh, Young Yang, Do-Young Yoon

引用次数: 0

Cereblon regulates the production of hepatic fibroblast growth factor 23 in diabetes. 脑龙调节糖尿病患者肝成纤维细胞生长因子 23 的产生。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-08

Seungwon An, Balachandar Nedumaran, Hangaram Oh, Taehyun Park, Chul-Seung Park, Ali R Djalilian, Sooyong Shin, Taehoon Chung, Yong Deuk Kim

引用次数: 0

Rice CHD3/Mi-2 chromatin remodeling factor RFS regulates vascular development and root formation by modulating the transcription of auxin-related genes NAL1 and OsPIN1. 水稻CHD3/Mi-2染色质重塑因子RFS通过调节辅助素相关基因NAL1和OsPIN1的转录来调控血管发育和根的形成。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-01

Hyeryung Yoon, Chaemyeong Lim, Bo Lyu, Qisheng Song, So-Yon Park, Kiyoon Kang, Sung-Hwan Cho, Nam-Chon Paek

{"title":"Rice CHD3/Mi-2 chromatin remodeling factor RFS regulates vascular development and root formation by modulating the transcription of auxin-related genes NAL1 and OsPIN1.","authors":"Hyeryung Yoon, Chaemyeong Lim, Bo Lyu, Qisheng Song, So-Yon Park, Kiyoon Kang, Sung-Hwan Cho, Nam-Chon Paek","doi":"","DOIUrl":"","url":null,"abstract":"The vascular system in plants facilitates long-distance transportation of water and nutrients through the xylem and phloem, while also providing mechanical support for vertical growth. Although many genes that regulate vascular development in rice have been identified, the mechanism by which epigenetic regulators control vascular development remains unclear. This study found that Rolled Fine Striped (RFS), a Chromodomain Helicase DNA-binding 3 (CHD3)/Mi-2 subfamily protein, regulates vascular development in rice by affecting the initiation and development of primordia. The rfs mutant was found to affect auxin-related genes, as revealed by RNA sequencing and reverse transcription-quantitative PCR analysis. The transcript levels of OsPIN1 and NAL1 genes were downregulated in rfs mutant, compared to the wild-type plant. The chromatin immunoprecipitation assays showed lower levels of H3K4me3 in the OsPIN1a and NAL1 genes in rfs mutant. Furthermore, exogenous auxin treatment partially rescued the reduced adventitious root vascular development in rfs mutant. Subsequently, exogenous treatments with auxin or an auxin-transport inhibitor revealed that the expression of OsPIN1a and NAL1 is mainly affected by auxin. These results provide strong evidence that RFS plays an important role in vascular development and root formation through the auxin signaling pathway in rice. [BMB Reports 2024; 57(10): 441-446].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifaceted roles of trained immunity in diverse pathological contexts. 训练有素的免疫力在不同病理情况下发挥着多方面的作用。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-01

Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim

引用次数: 0

Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells. 通过消耗 PDIA6 增加ER应激会损害肾细胞的初级纤毛生成并提高其对铁凋亡的敏感性。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-01

Joon Bum Kim, Hyejin Hyung, Ji-Eun Bae, Soyoung Jang, Na Yeon Park, Doo Sin Jo, Yong Hwan Kim, Dong Kyu Choi, Hong-Yeoul Ryu, Hyun-Shik Lee, Zae Young Ryoo, Dong-Hyung Cho

{"title":"Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells.","authors":"Joon Bum Kim, Hyejin Hyung, Ji-Eun Bae, Soyoung Jang, Na Yeon Park, Doo Sin Jo, Yong Hwan Kim, Dong Kyu Choi, Hong-Yeoul Ryu, Hyun-Shik Lee, Zae Young Ryoo, Dong-Hyung Cho","doi":"","DOIUrl":"","url":null,"abstract":"Primary cilia are crucial for cellular balance, serving as sensors for external conditions. Nephronophthisis and related ciliopathies, which are hereditary and degenerative, stem from genetic mutations in cilia-related genes. However, the precise mechanisms of these conditions are still not fully understood. Our research demonstrates that downregulating PDIA6, leading to cilia removal, makes cells more sensitive to ferroptotic death caused by endoplasmic reticulum (ER) stress. The reduction of PDIA6 intensifies the ER stress response, while also impairing the regulation of primary cilia in various cell types. PDIA6 loss worsens ER stress, hastening ferroptotic death in proximal tubule epithelial cells, HK2 cells. Counteracting this ER stress can mitigate PDIA6 depletion effects, restoring both the number and length of cilia. Moreover, preventing ferroptosis corrects the disrupted primary ciliogenesis due to PDIA6 depletion in HK2 cells. Our findings emphasize the role of PDIA6 in primary ciliogenesis, and suggest its absence enhances ER stress and ferroptosis. These insights offer new therapeutic avenues for treating nephronophthisis and similar ciliopathies. [BMB Reports 2024; 57(10): 453-458].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1). 异三聚驱动蛋白-2 家族成员 KIF3A 可直接与残疾-1（Dab1）结合。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-01

Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog

{"title":"The heterotrimeric kinesin-2 family member KIF3A directly binds to disabled-1 (Dab1).","authors":"Myoung Hun Kim, Young Joo Jeong, Sang-Hwa Urm, Dae-Hyun Seog","doi":"","DOIUrl":"","url":null,"abstract":"The heterotrimeric molecular motor kinesin-2 is involved in the microtubule-dependent transport of intracellular cargo. It consists of two distinct motor subunits (KIF3A, and KIF3B) and a non-motor subunit, kinesin-associated protein 3 (KAP3). The cargo-binding domain (CBD) at the carboxyl (C)-terminus of KIF3s plays an important role in the interaction with several different binding proteins. To identify the binding proteins for heterotrimeric kinesin-2, we performed a yeast two-hybrid screen and found a new interaction with Disables-1 (Dab1), the intracellular adaptor protein of reelin receptors. Dab1 bound to the CBD of KIF3A, but did not interact with the C-terminal domain of KIF3B, KIF5B, KIF17 or KAP3. The phosphotyrosine binding (PTB) domain-containing region of Dab1 is essential for the interaction with KIF3A. KIF3A interacted with GST-Dab1, and GST-CaMKIIα, but did not interact with GST-apolipoprotein E receptor 2 (ApoER2)-C or with GST alone. When co-expressed in HEK-293T cells, Dab1 co-precipitated with KIF3A, but not with KIF5B. Dab1 and KIF3A were co-localized in cultured cells. We also identified deduced cell surface expression of ApoER2 in KIF3A dominant-negative cells. These results suggest that the KIF3A plays a role in the intracellular trafficking of ApoER2 to the cell surface. [BMB Reports 2024; 57(10): 447-452].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma. 抑制 P2RX7 可抑制糖酵解和 AKT 在人肝细胞癌中的激活，从而增加细胞毒性。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-10-01

Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon

{"title":"Inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human hepatocellular carcinoma.","authors":"Jae Kook Yang, Junhyung Kim, Young Hyeon Ahn, Sang Ho Bae, Moo-Jun Baek, Sae Hwan Lee, Jong-Seok Moon","doi":"","DOIUrl":"","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. HCC occurs people with chronic liver diseases. The purinergic receptor P2X 7 (P2RX7) is involved in tumor proliferation and growth. Also, P2RX7 is associated with tumor invasion and metastatic dissemination. High glucose utilization is important for the survival of various types of tumors. However, the role of P2RX7 in glucose metabolism and cellular survival of HCC remains unclear. Here, our results show that the gene and protein levels of P2RX7 were elevated in tumor cells of patients with HCC. The pharmacological inhibition of P2RX7 by A-804598, a selective P2RX7 antagonist, and genetic inhibition by P2RX7 knockdown suppressed the glycolytic activity by reduction of hexokinase 2 (HK2), a key enzyme of the glycolysis pathway, in human HCC cells. Also, both A-804598 treatment and P2RX7 knockdown induced cytotoxicity via inhibition of AKT activation which is critical for tumor cell survival in human HCC cells. Moreover, A-804598 treatment and P2RX7 knockdown increased cytotoxicity and caspase-3 activation in human HCC cells. These results suggest that inhibition of P2RX7 contributes to cytotoxicity by suppression of glycolysis and AKT activation in human HCC. [BMB Reports 2024; 57(10): 459-464].","PeriodicalId":9010,"journal":{"name":"BMB Reports","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluorescence-based techniques for investigating estrogen receptor dynamics. 基于荧光的雌激素受体动态研究技术。

IF 2.9 3区生物学

BMB Reports Pub Date : 2024-09-02

Kiseok Han, Gyuho Choi, Tae-Jin Kim

引用次数: 0

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