JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
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2024
·Vol. 150
·期 7
·1-19
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IF 2.7
Chang Jing-Xia,Zhang Meng,Lou Li-Li,Chu He-Ying,Wang Hua-Qi
Purpose Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/β-catenin pathway. Methods Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo. Results In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the β-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells. Conclusion KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate LUAD cell invasion and metastasis.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
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2013
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IF 5.056
Yadong Hu,Helin Wang,Qingtao Wang,Haiteng Deng
Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in all living cells and mediates multiple cellular signaling pathways. In the present study, a 35% decrease of cellular NAD level is achieved by stable expression of the N-terminal truncated CD38, a NAD hydrolase. CD38-expressing (CD38(+)) cells have the lower growth rate and are more susceptive to oxidative stress than the wild type cells and empty vector-transfected (CD38(−)) cells. Quantitative proteomic analysis shows that 178 proteins are down-regulated in CD38(+) cells, which involve in diverse cellular processes including glycolysis, RNA processing and protein synthesis, antioxidant, and DNA repair. Down regulation of six selected proteins is confirmed by Western blotting. However, down-regulation of mRNA expressions of genes associated with glycolysis, antioxidant, and DNA repair is less significant than the corresponding change in protein expression, suggesting the low NAD level impairs the protein translational machinery in CD38(+) cells. Down-regulation of antioxidant protein and DNA-repair protein expression contributes to the susceptibility of CD38(+) cells to oxidative stress. Taken together, these results demonstrate that CD38(+) cells are a useful model to study effects of the cellular NAD levels on cellular processes and establish a new linker between cellular NAD levels and oxidative stress.
研究领域:
分子生物学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
MOLECULAR CELL
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2024
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IF 14.5
Yu-Meng Sun,Shun-Xin Zhu,Xiao-Tong Chen,Qi Pan,Yan An,Tian-Qi Chen,Heng-Jing Huang,Ke-Jia Pu,Jun-Yi Lian,Wen-Long Zhao,Wen-Tao Wang,Yue-Qin Chen
Liquid-to-solid phase transition of proteins with prion-like domains (PLDs) has been associated with neurodegenerative diseases and aging. High protein concentration is one important aspect triggering the transition; however, several prion-like proteins, including fibrillarin (FBL), an important phase-separated protein in the nucleolus for pre-rRNA processing, show relatively high expression levels in certain cells, especially cancer cells, without obvious phase transitions and growth arrest. How cells maintain prion-like protein proteostasis is still unknown. Here, we attempt to answer the question, with FBL as an example. We find that lncRNA DNAJC3-AS1 can buffer the behavior of FBL condensation and maintain the state and function of fibrillar component/dense fibrillar component (FC/DFC) units in human cell lines through two mechanisms, not only facilitating FBL condensation but also inhibiting excessive aggregation by binding multiple PLDs and partially blocking their interactions. We propose that lncRNAs could supply buffered systems to sustain functional phase states of prion-like proteins.
研究领域:
分子生物学
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细胞生物学
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遗传学
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癌症研究
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Luyu Qi,Jun Zhu,Zhongyi Cheng,Zhiyi Yuan,Wulin Qi,JiaHuan Wu,Yifeng Qin,Jingbo Yang,Tao Luo,Minkun Wang,Yejing Weng,Jianzhong Shao
Protein phosphorylation, a widely occurring and significant post-translational modification, is integral to various biological processes. We previously utilized a protein affinity probe to identify genes damaged by cisplatin, revealing that it inflicts substantial damage on protein kinase and protein phosphatase genes. In this study, we investigated cisplatin-induced alterations in the global proteome and phosphoproteome of A549 cells. Employing Fe-IMAC beads and tyrosine phosphorylation enrichment antibodies, we identified 6944 protein groups and 18,274 phosphorylation sites on 4915 proteins across three biological replicates of both cisplatin-treated A549 cells and control cells. Among these, 730 tyrosine phosphorylation sites were identified—marking the most substantial discovery of such sites in A549 cells following cisplatin treatment. Bioinformatics analysis indicated that the proteins exhibiting significant phosphorylation level changes predominantly involved in RNA processing, modification, transcription, translation, and the spliceosome. This suggests that cisplatin-induced damage to protein kinases and phosphatases may disrupt the normal function of these proteins, consequently impairing DNA replication, RNA translation, and shearing, ultimately culminating in tumor cell death. Moreover, we cross-referenced our proteomic data with our previously obtained cisplatin-damaged genes, observing that the majority of down-regulated proteins derived from cisplatin-induced gene damage. The data are available on ProteomeXchange under the identifier PXD053902.
研究领域:
癌症生物学
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分子生物学
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蛋白质组学
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磷酸蛋白质组学
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生物信息学
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
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IF 8.2
Jiansong Liu,Shuo Wang,Changyu Tao,Haoyun Liu,Yutong Mao,Xinhui Zhao,Kaiqi Cheng,Guanqun Mu,Meng Wang,Weibin Wang,Ence Yang,Jiadong Wang,Yang Yang
Peroxisomes are essential organelles that maintain cellular redox homeostasis. Although alternatively spliced variants of certain peroxisome-related genes have been identified, the regulatory mechanisms governing alternative splicing (AS) and its functional impact on peroxisomal redox homeostasis remain poorly understood. Here, we demonstrate that glucose starvation (GS) induces crotonylation of DEAD-box helicase 1 (DDX1), which is regulated by the crotonyltransferase general control non-repressed protein 5 (GCN5) and the decrotonylase histone deacetylase 1 (HDAC1). DDX1 crotonylation at the lysine 490 residue enhances its interaction with heterogeneous nuclear ribonucleoprotein K (HNRNPK), which mediates mutually exclusive AS of acyl-CoA oxidase 1 (ACOX1). The AS of ACOX1, driven by DDX1 crotonylation and HNRNPK, promotes the generation of peroxisomal ROS, thereby enhancing oxidative damage and ultimately suppressing colorectal cancer (CRC) cell proliferation. Our findings uncover a novel mechanism by which DDX1 crotonylation regulates the AS of peroxisome-related genes and mediates peroxisomal redox homeostasis. This discovery bridges a critical gap in our understanding of how posttranslational modifications (PTMs) of DEAD/DEXD box RNA helicases modulate gene AS and identifies a potential therapeutic target for colorectal cancer.
研究领域:
分子生物学
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癌症生物学
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细胞生物学
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RNA加工
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表观遗传学
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氧化还原生物学
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DOI
PubMed
高影响因子
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