Review
Oncology
Diana Gulei, Rares Drula, Gabriel Ghiaur, Anca Dana Buzoianu, Yelena Kravtsova-Ivantsiv, Ciprian Tomuleasa, Aaron Ciechanover
Summary: The ubiquitin-proteasome system (UPS) is crucial for protein degradation, and its dysregulation is closely related to malignant pathologies. KPC1, an E3 ubiquitin ligase component, plays a key role in cancer by regulating p27 signaling and the NF-xB pathway. KPC1 maintains the ubiquitination of cytoplasmic p27, influencing cell-cycle progression, and also induces the ubiquitination of p105 to control NF-xB signaling. Therapeutic reinforcement of the KPC1-p50 axis shows promising tumor suppressor activity in multiple malignancies.
Article
Multidisciplinary Sciences
Brian DeVeale, Leqian Liu, Ryan Boileau, Jennifer Swindlehurst-Chan, Bryan Marsh, Jacob W. Freimer, Adam Abate, Robert Blelloch
Summary: This study reveals the cell cycle structure of pluripotent embryonic stem cells and the relationship between G1/S restriction point, gene expression, and cellular differentiation. By genetically manipulating G1/S restriction point regulators miR-302 and P27, the researchers found that they can accelerate or delay the onset of phasic gene expression in mouse embryos. Additionally, loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a mutated Cyclin E blocks it. These findings provide new insights into our understanding of cellular differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Kun Zhang, Kaizhao Hu, Qian Li, Min Li, Ke Gao, Kecheng Yang, Bing Zhao, Xiao-Jing Shi, Lirong Zhang, Hong-Min Liu
Summary: Skp2 is a component of cullin-RING ligases, and its high expression is associated with aggressive tumor tissues and poor prognosis. In this study, a series of new Skp2 inhibitors were synthesized and their structure-activity relationship was systematically studied. Among them, compound 14i showed potent activity against Skp2 and exhibited effective anticancer effects on PC-3 and MGC-803 cells as well as xenograft mouse models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Cell Biology
Dexin Shen, Lingao Ju, Fenfang Zhou, Mengxue Yu, Haoli Ma, Yi Zhang, Tongzu Liu, Yu Xiao, Xinghuan Wang, Kaiyu Qian
Summary: Melatonin, as a potential therapy for prostate cancer, has significant antioxidant and anticancer abilities. Studies have shown that melatonin can inhibit the development of prostate cancer through different pathways, and the synergistic use with other drugs may have better effects.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Multidisciplinary Sciences
Chao Zhang, Xin Wang, Chuanbao Zhang
Summary: CDK2 was identified as the direct target of icaritin in tumor cells. Icaritin interacted with CDK2, resulting in downregulation of CDK2 activity and interference with complex formation. Additionally, icaritin modulated microRNA-597 expression, which reduced the stability and translation efficiency of CDK2-mRNA. In vitro and in vivo experiments demonstrated that icaritin inhibited proliferation and promoted apoptosis of tumor cells, similar to CDK2 inhibitor k03861.
Article
Biochemistry & Molecular Biology
Ji Wang, Zongyu Xiao, Peng Li, Chunwang Wu, Yan Li, Qing Wang, Yanming Chen, Honglong Zhou, Zhi Li, Zhaotao Wang, Qing Lan, Yezhong Wang
Summary: PRMT6, a type I arginine methyltransferase, asymmetrically di-methylates the arginine residues of both histones and non-histones. Increasing evidence indicates that PRMT6 plays a tumor mediator involved in human malignancies. Investigation of PRMT6 expression in glioma tissues demonstrated that PRMT6 is overexpressed, and elevated expression of PRMT6 is negatively correlated with poor prognosis in glioma/GBM patients. Silencing PRMT6 inhibited GBM cell proliferation and induced cell cycle arrest at the G0/G1 phase, while overexpressing PRMT6 had opposite results.
Article
Multidisciplinary Sciences
Caleb K. Stubbs, Marco Biancucci, Vania Vidimar, Karla J. F. Satchell
Summary: RRSP has the ability to inactivate all isoforms of RAS and major oncogenic KRAS mutants, with varying outcomes in terms of cell fate within different colorectal cancer cell lines. While some cell lines undergo apoptosis upon RRSP treatment, others experience G1 cell cycle arrest. Additionally, RRSP may affect cell growth through the rescued expression of tumor suppressor protein p27 (Kip1) in certain cell lines.
SCIENTIFIC REPORTS
(2021)
Article
Pathology
Ken Sasai, Kouichi Tabu, Takashi Saito, Yukio Matsuba, Takaomi C. Saido, Shinya Tanaka
Summary: GLI1 is able to transform immortalized human astrocytes, while FOXM1 fails to induce malignant transformation. The downregulation of p27(KIP1) contributes to the malignant features of transformed astrocytes. Models using immortalized/transformed astrocytes are useful for identifying essential changes required for glioma formation.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Multidisciplinary Sciences
Manuel Kaulich, Verena M. Link, John D. Lapek, Yeon J. Lee, Christopher K. Glass, David J. Gonzalez, Steven F. Dowdy
Summary: The study identified the regulatory role of cyclin D:Cdk4/6 in early G1 phase in controlling cell cycle entry timing, characterized a phosphorylation gradient and substrate identity in early G1 phase, and explored novel substrates connecting early G1 phase functions with cyclin E:Cdk2 activation and Rb inactivation by hyper-phosphorylation.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Jolien Beeken, Sofie Kessels, Jean-Michel Rigo, Yeranddy A. Alpizar, Laurent Nguyen, Bert Brone
Summary: p27(kip1) plays a role in regulating morphological complexity in microglia and affects phagocytic uptake of synaptosomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Cheng-Han Tsai, Chun-Yuan Chang, Bing-Ze Lin, Yu-Lou Wu, Meng-Hsiu Wu, Liang-Tin Lin, Wen-Chien Huang, Jonathan D. Holz, Tzong-Jen Sheu, Jhih-Shian Lee, Richard N. Kitsis, Pei-Han Tai, Yi-Jang Lee
Summary: The study found that cofilin-1 plays a crucial role in cell senescence by affecting morphological changes and cell enlargement. It induces cell senescence through the regulation of p27(Kip1), independent of p53 and p16(INK4) expressions. Additionally, cofilin-1 upregulation can also induce the expression of p27(Kip1) by suppressing the TEAD1 transcription factor, which in turn leads to senescence-related phenotypes.
Article
Biochemistry & Molecular Biology
Xiaohong Xia, Xiaolin Liu, Renjie Chai, Qiong Xu, Zhenyu Luo, Jielei Gu, Yangshuo Jin, Tumei Hu, Cuifu Yu, Bijun Du, Hongbiao Huang, Wenchao Ou, Shiming Liu, Ningning Liu
Summary: This study found that USP10 is involved in vascular remodeling by directly promoting VSMC proliferation and migration via stabilization of Skp2 protein expression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Ana Garcia-Osta, Jinya Dong, Maria Jesus Moreno-Aliaga, Maria Javier Ramirez
Summary: The cell cycle is regulated by factors such as p27(Kip1), which controls different functions in the nucleus and cytoplasm. In Alzheimer's disease, alterations to cell cycle events and increased neurogenesis have been observed, suggesting a role for p27(Kip1) in the disease process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Yilin Fan, Tobias Meyer
Summary: Cell density and mitogen signals compete to regulate the levels of cyclin D1 and p27, determining whether cells proliferate or enter quiescence. The history of competing signals experienced by mother cells is funneled into a precise activator-inhibitor balance that controls the fate of daughter cells.
Article
Biochemistry & Molecular Biology
Shudong Niu, Kaixin Cheng, Longzhong Jia, Jing Liang, Lu Mu, Yibo Wang, Xuebing Yang, Chen Yang, Yan Zhang, Chao Wang, Lijun Huang, Huarong Wang, Shuang Zhang, Hua Zhang
Summary: This study demonstrated that ovarian granulosa cell tumors (GCTs) originate from mutant granulosa cells (GCs) and identified the upregulation of immune evasion genes Cd24a and Cd47 as a mechanism for the transition of mutant GCs to GCTs. Treatment with the Cd47 inhibitor RRX-001 effectively suppressed GCT growth in vivo.
CELL DEATH AND DIFFERENTIATION
(2023)