Article
Oncology
Irina Jilishitz, Jason Luis Quinones, Priyank Patel, Grace Chen, Jared Pasetsky, Allison VanInwegen, Scott Schoninger, Manasi P. Jogalekar, Vladislav Tsiperson, Lingyue Yan, Yun Wu, Susan R. S. Gottesman, Jonathan Somma, Stacy W. Blain
Summary: Using NP-ALT as a therapeutic approach can effectively inhibit CDK4/6 and CDK2 by targeting the tyrosine phosphorylation of p27Kip1. This treatment shows efficacy in HR+ breast cancer cells, CDK4i-resistant cells, and can induce necroptosis, particularly in cells with an ER gain of function mutation.
MOLECULAR CANCER RESEARCH
(2021)
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
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
Oncology
Severine Isabelle Gharbi, Laura A. Pelletier, Alfonso Espada, Jesus Gutierrez, Sonia Maria Gutierrez Sanfeliciano, Charles T. Rauch, Maria Patricia Ganado, Carmen Baquero, Elisabet Zapatero, Aiping Zhang, Jordi Benach, Anna-Maria Russell, Leticia Cano, Sandra Gomez, Howard Broughton, Nicholas Pulliam, Carmen Maria Perez, Raquel Torres, Marjoke F. Debets, Alfonso de Dios, Oscar Puig, Mark T. Hilgers, Maria Jose Lallena
Summary: This study provides insights into the mechanism of CDK4/6 inhibitors, showing that CDK4/6i can stabilize the mature CDK4-cyclin D complex and selectively displace p21. Prolonged binding of abemaciclib to CDK4 leads to potent cell cycle inhibition in breast cancer cell lines and prevents rebound activation of downstream signaling.
Article
Cell Biology
Ada Nowosad, Justine Creff, Pauline Jeannot, Raphael Culerrier, Patrice Codogno, Stephane Manenti, Laurent Nguyen, Arnaud Besson
Summary: In response to glucose starvation, p27 promotes autophagy by facilitating autophagosome trafficking along microtubule tracks via maintaining elevated microtubule acetylation through an ATAT1-dependent mechanism.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Jorge Gomez Tejeda Zanudo, Pingping Mao, Clara Alcon, Kailey Kowalski, Gabriela N. Johnson, Guotai Xu, Jose Baselga, Maurizio Scaltriti, Anthony Letai, Joan Montero, Reka Albert, Nikhil Wagle
Summary: The study utilized a network-based mathematical model to predict effective drug combinations for treating ER+ breast cancer with PI3K alpha inhibitors, which was experimentally validated and revealed potential resistance mechanisms and sensitivity regulators.
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
Cell Biology
Hsuan-Hsiang Peng, Hao-Chin Yang, Darius Rupa, Chun-Han Yen, Ya-Wen Chiu, Wei-Jia Yang, Fuh-Jinn Luo, Ta-Chun Yuan
Summary: This study investigated the oncogenic role of ACK1 and its underlying molecular mechanism in head and neck squamous cell carcinoma. The results demonstrated that ACK1 is highly expressed in HNSCC tumors and promotes cell proliferation by phosphorylating and degrading p27.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2022)
Article
Multidisciplinary Sciences
Rhianna J. Rowland, Richard Heath, Daniel Maskell, Rebecca F. Thompson, Neil A. Ranson, James N. Blaza, Jane A. Endicott, Martin E. M. Noble, Marco Salamina
Summary: p27KIP1, a member of the CIP/KIP family, regulates the cell cycle by inhibiting CDKs. It is phosphorylated by CDK1/2 and recruited to the SCFSKP2 E3 ubiquitin ligase complex for degradation. The crystal structure of the SKP1-SKP2-CKS1-p27 phosphopeptide revealed the binding mode of p27 to SKP2 and CKS1. The experimental structure of the isolated CDK2-cyclin A-CKS1-p27-SKP1-SKP2 complex was determined using cryogenic electron microscopy.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Lon W. R. Fong, Jangsoon Lee, Hui-Kuan Lin, Naoto T. Ueno, Shuxing Zhang
Summary: The ubiquitination of SKP2, an oncoprotein, is regulated by E3 ligases and deubiquitinases. A two-gene signature involving FZR1 and USP10 was identified to reflect the activity level of SKP2. This signature stratifies breast cancer patients into two groups with distinct protein levels of SKP2 ubiquitination substrate p27 and recapitulates the expression patterns of SKP2. The signature is also strongly associated with clinical outcome and tumor characteristics.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Tian Lan, Meng Yu, Weisheng Chen, Jun Yin, Hsiang-Tsun Chang, Shan Tang, Ye Zhao, Spyros Svoronos, Samuel W. K. Wong, Yiider Tseng
Summary: The study demonstrates that cell morphology and dynamic subcellular behavior are homogeneous within each stage of the cell cycle phases but heterogeneous between phases. It reveals the relationship between the cell cycle and cell migration through quantitative cell analyses and interactive molecular mechanisms, with potential implications in countering drug resistance.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Evangelia Papadimitriou, Vasiliki K. Kanellopoulou
Summary: Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is highly expressed during embryonic development but limited in adulthood. It plays a role in oligodendrocytes' survival and maturation in the central nervous system. In gliomas, PTPRZ1 is significantly upregulated and studied as a potential cancer driver and therapy target. However, its functional significance and tumor-suppressor role in other cancer types need further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
QinLei Gu, Kenneth S. Tung, Ulrike M. Lorenz
Summary: To achieve a healthy and functional immune system, there is a delicate balance between the activation of Tcon cells and the suppression by Treg cells. SHP-1 plays a role in modulating this balance by regulating Tcon cell resistance to Treg-mediated suppression. However, the role of SHP-1 in Treg function is still not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Adrienn Markovics, Sydney Lupo, Niyati Patel, Katalin Mikecz, D. Rick Sumner, Ryan D. Ross
Summary: This study found that Shp1 overexpression leads to increased bone mass and improved mechanical properties in mice, but only in 28-day-old mice. Female SHP1-Tg mice showed higher trabecular bone volume, trabecular number, and connectivity density compared to wildtype mice.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Article
Immunology
Lei Shi, Zhen Bian, Koby Kidder, Hongwei Liang, Yuan Liu
Summary: Macrophage functional plasticity is crucial in responding to proinflammatory stimuli. SIRP alpha serves as a key negative regulator of proinflammatory macrophage polarization by activating SHP-1 and inhibiting Akt2, leading to decreased proinflammatory cytokine production and Ag presentation machinery expression.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
J. Mueller-Deile, H. Schenk, M. Schiffer
Article
Urology & Nephrology
Christoph Kuppe, Katja Leuchtle, Anton Wagner, Nazanin Kabgani, Turgay Saritas, Victor G. Puelles, Bart Smeets, Samy Hakroush, Johan van der Vlag, Peter Boor, Mario Schiffer, Hermann-Josef Grone, Agnes Fogo, Juergen Floege, Marcus Johannes Moeller
KIDNEY INTERNATIONAL
(2019)
Article
Urology & Nephrology
J. Mueller-Deile, H. Schenk, P. Schroder, K. Schulze, P. Bolanos-Palmieri, F. Siegerist, N. Endlich, H. Haller, M. Schiffer
KIDNEY INTERNATIONAL
(2019)
Article
Cell Biology
Janina Mueller-Deile, Jan Dannenberg, Peidi Liu, Johan Lorenzen, Jenny Nystrom, Thomas Thum, Mario Schiffer
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2019)
Article
Health Care Sciences & Services
Georgios Paslakis, Josefine Fischer-Jacobs, Lars Pape, Mario Schiffer, Raoul Gertges, Uwe Tegtbur, Tanja Zimmermann, Mariel Noehre, Martina de Zwaan
JOURNAL OF MEDICAL INTERNET RESEARCH
(2019)
Article
Urology & Nephrology
Kristina M. Niculovic, Linda Blume, Henri Wedekind, Elina Kats, Iris Albers, Stephanie Groos, Markus Abeln, Jessica Schmitz, Esther Beuke, Jan H. Braesen, Anette Melk, Mario Schiffer, Birgit Weinhold, Anja K. Muenster-Kuehnel
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2019)
Article
Pediatrics
Asaf Vivante, Orna Staretz Chacham, Shirlee Shril, Ruth Schreiber, Shrikant M. Mane, Ben Pode-Shakked, Neveen A. Soliman, Irene Koneth, Mario Schiffer, Yair Anikster, Friedhelm Hildebrandt
PEDIATRIC NEPHROLOGY
(2019)
Article
Urology & Nephrology
Irini Tossidou, Beina Teng, Kirstin Worthmann, Janina Mueller-Deile, Tilman Jobst-Schwan, Christian Kardinal, Patricia Schroder, Patricia Bolanos-Palmieri, Hermann Haller, Jonas Willerding, Dana M. Drost, Laura de Jonge, Thomas Reubold, Susanne Eschenburg, Ruth Johnson, Mario Schiffer
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2019)
Article
Psychiatry
Felix Klewitz, Mariel Noehre, Maximilian Bauer-Hohmann, Uwe Tegtbur, Lena Schiffer, Lars Pape, Mario Schiffer, Martina de Zwaan
FRONTIERS IN PSYCHIATRY
(2019)
Article
Multidisciplinary Sciences
H. Schenk, J. Mueller-Deile, P. Schroder, P. Bolanos-Palmieri, L. Beverly-Staggs, R. White, J. H. Braesen, H. Haller, M. Schiffer
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Johanna Protze, Stephanie Naas, Rene Krueger, Christine Stoehr, Andre Kraus, Steffen Grampp, Michael Wiesener, Mario Schiffer, Arndt Hartmann, Bernd Wullich, Johannes Schoedel
Summary: The evolution of clear cell renal cell carcinoma is influenced by dysregulation of HIF pathways due to loss of the von Hippel-Lindau tumor suppressor protein. Polymorphisms associated with renal cell carcinoma affect HIF-DNA interactions, impacting the risk of developing renal cancer. A specific SNP on chr14q.24.2 in DPF3 has been linked to RCC and was found to create a novel HIF-binding motif, affecting DPF3 expression and potentially increasing the risk of renal cancer development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Cell Biology
Stephanie Naas, Mario Schiffer, Johannes Schoedel
Summary: Renal fibrosis is the final stage of kidney diseases and has a significant impact on patients’ quality of life and survival. Factors such as inflammation, metabolic stress, and hypoxia contribute to the progression of renal fibrosis. Hypoxia-inducible factors have both pro- and antifibrotic effects in acute and chronic kidney diseases. Recent advancements in sequencing technologies provide new insights into the cell type-specific effects of hypoxia on the progression of renal fibrosis, particularly in humans.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Lena Schiffer, Melanie Hartleib-Otto, Christian Lerch, Hermann Haller, Lars Pape, Mario Schiffer
Article
Urology & Nephrology
Marwin Groener, Ying Wang, Elizabeth Cross, Xuefei Tian, Karen Ebenezer, Eunice Baik, Christopher Pedigo, Mario Schiffer, Kazunori Inoue, Shuta Ishibe
Article
Psychology, Multidisciplinary
Daria Tkachenko, Laura Franke, Luisa Peters, Mario Schiffer, Tanja Zimmermann
FRONTIERS IN PSYCHOLOGY
(2019)