Review
Gastroenterology & Hepatology
Benno Traub, Aileen Roth, Marko Kornmann, Uwe Knippschild, Joachim Bischof
Summary: Pancreatic cancer is a devastating disease with poor survival rates, prompting the need for new therapeutic approaches. Protein kinases play crucial roles in development and pathogenesis, making them potential targets for precision medicine in patients with deregulated kinase pathways.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eric Hawley, Jeffrey Gehlhausen, Sofiia Karchugina, Hoi-Yee Chow, Daniela Araiza-Olivera, Maria Radu, Abbi Smith, Ciersten Burks, Li Jiang, Xiaohong Li, Waylan Bessler, Andrea Masters, Donna Edwards, Callie Burgin, David Jones, Charles Yates, D. Wade Clapp, Jonathan Chernoff, Su-Jung Park
Summary: The study revealed that PAK1 and PAK2 are hyper activated in Merlin-deficient murine schwannomas, but inhibitors had limited efficacy. Genetic ablation of Pak1 reduced tumor formation, suggesting PAK1 as a potential therapeutic target for vestibular schwannomas.
HUMAN MOLECULAR GENETICS
(2021)
Article
Oncology
Husain Yar Khan, Md. Hafiz Uddin, Suresh Kumar Balasubramanian, Noor Sulaiman, Marium Iqbal, Mahmoud Chaker, Amro Aboukameel, Yiwei Li, William Senapedis, Erkan Baloglu, Ramzi M. Mohammad, Jeffrey Zonder, Asfar S. Azmi
Summary: Targeting PAK4 and NAMPT using the small molecule inhibitor KPT-9274 can inhibit cell proliferation, deplete energy, and induce apoptosis in various NHL subtypes. KPT-9274 treatment shows potent anti-tumor effects in experimental models, suggesting its potential as a novel therapy for NHL.
Article
Chemistry, Medicinal
Nora Chouha, Hussein Abou-Hamdan, Hajime Yurugi, Riku Yoshii, Hiromi Ii, Ahmad Najem, Ghanem E. Ghanem, Susumu Nakata, Krishnaraj Rajalingam, Yu Peng, Dong Wang, Canan G. Nebigil, Laurent Desaubry
Summary: This study reports the structural requirements of fluorizoline analogues for their activities. Some compounds were found to have enhanced anti-C-RAF and anti-MEK activities, and higher cytotoxicity in HeLa cells compared to fluorizoline. These findings provide a foundation for further optimization of PHB ligands for cancer treatment and the discovery of a new chemical tool to study PHB signaling in cancers and other diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Mohankumar Amirthalingam, Sundararaj Palanisamy, Shinkichi Tawata
Summary: PAKs are a group of kinases involved in a wide range of cellular functions and have been implicated as not only oncogenic but also aging kinases. Targeting PAKs could be a potential strategy for cancer therapy development with minimal side effects and promoting healthy longevity.
AGEING RESEARCH REVIEWS
(2021)
Article
Oncology
Shengchen Su, Sungyong You, Yanping Wang, Patrick Tamukong, Michael J. Quist, Catherine S. Grasso, Hyung L. Kim
Summary: Antitumor immunity requires lymphocytes to localize to the tumor. Prostate cancers (PCs) are immunologically cold and tend to lack T-cell infiltration. Most advanced PCs are insensitive to PD1 blockade therapies.
Article
Cell Biology
Mayank Maheshwari, Nisha Yadav, Mohammad Hasanain, Praveen Pandey, Rohit Sahai, Kuldeep Choyal, Akhilesh Singh, Mushtaq A. Nengroo, Krishan K. Saini, Deepak Kumar, Kalyan Mitra, Dipak Datta, Jayanta Sarkar
Summary: The article discusses the dual function of p21 in cancer, with both inhibitory and oncogenic effects. Specifically, p21 negatively regulates basal autophagy and has oncogenic activity during early tumor development, while its inhibition promotes survival and growth of established tumors.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Kaifan Zhang, Yan Wang, Tianda Fan, Cheng Zeng, Zhong Sheng Sun
Summary: PAKs are main effectors of the Rho GTPases Cdc42 and Rac, linking complex cytoskeletal networks to neural activity. They play a crucial role in neuronal development, dendritic spine plasticity, and are implicated in neurodevelopmental and neurodegenerative disorders. Comprehensive understanding of PAKs' role in neural cytoskeletal remodeling can enhance our knowledge of neurological diseases and potentially provide therapeutic targets.
Review
Biochemistry & Molecular Biology
Ashwin K. Chetty, Byung Hak Ha, Titus J. Boggon
Summary: This review focuses on the signaling pathways mediated by Rho family small GTPases and the specific roles of type II PAKs. The selectivity of Rho GTPases for PAK family members and the molecular basis for substrate recognition and regulation of signaling are discussed. The cross talk between Rho family small GTPases and the involvement of PAKs in diseases are also addressed.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kai Zheng, Zhe Ren, Yifei Wang
Summary: Accumulating evidence has confirmed the interaction between viral infection and host alternative splicing. Serine-arginine (SR) proteins and serine-arginine protein kinases (SRPKs) play critical roles in spliceosome maturation, alternative splicing, and RNA metabolism. Viral proteins, as well as other cytoplasmic proteins, have been identified as substrates of SRPKs, highlighting the importance of SRPKs in virus-host interactions. This review discusses the regulation and biological function of SRPKs, their involvement in viral infection processes, the structure-function relationships of SRPK inhibitors, and the potential of targeting viral proteins and cellular substrates of SRPKs for antiviral therapy.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Toxicology
Ping Guo, Yufeng Liu, Jingrong Feng, Shihang Tang, Fanyan Wei, Jian Feng
Summary: In this review, the importance of PAK1 in cardiac diseases, especially in the regulation of programmed cell death, oxidative stress, and inflammatory responses of cardiomyocytes, is discussed. The association of PAK1 with the gut microbiome and microRNAs in cardiotoxicity is also introduced.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Cell Biology
Yiming Ding, Hanjie Liu, Chuanbao Zhang, Zhaoshi Bao, Shuqing Yu
Summary: The study investigated the expression and prognostic relevance of PLKs in GBM patients, revealing potential molecular indicators and treatment targets. It was found that PLK2 expression is linked to patient outcomes in GBM, with the PLK2 inhibitor ON1231320 showing anticancer effects in glioma cells. The findings suggest a promising direction for future research on PLK inhibitors.
Review
Genetics & Heredity
Ester Molina, Linda Hong, IIana Chefetz
Summary: LKB1 and AMPK alpha play crucial roles in cancer development by sensing and regulating energy requirements in tumor cells. In addition to these, there are multiple AMPK-like downstream targets of LKB1 involved in various cellular processes such as cell cycle progression, cell polarity, metabolism, and mitotic regulation.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Clinical Neurology
Cathal John Hannan, Charlotte Hammerbeck-Ward, Omar Nathan Pathmanaban, Miriam J. Smith, Scott A. A. Rutherford, Simon K. K. Lloyd, Simon Richard Mackenzie Freeman, Andrew J. Wallace, Andrew Thomas King, Dafydd Gareth Richard Evans
Summary: Patients presenting with unilateral vestibular schwannomas (UVS) and multiple meningiomas (MM) are more likely to be diagnosed with neurofibromatosis type 2 (NF2) compared to patients with UVS and multiple nonintradermal schwannomas (NIDS), but less likely to develop bilateral vestibular schwannomas. Some patients with MM without meeting NF2 criteria have pathogenic variants in SMARCE1 and mosaic NF2.
Review
Biochemistry & Molecular Biology
Laura Garcia-Hernandez, Maria Belen Garcia-Ortega, Gloria Ruiz-Alcala, Esmeralda Carrillo, Juan Antonio Marchal, Maria angel Garcia
Summary: The MAPK family plays a crucial role in transducing signals in cellular responses, including cancer. Among this family, p38 kinases have been found altered in various diseases and often have opposing mechanisms in cancer. The different isoforms of p38 have extensive regulation and potential as biomarkers and molecular targets. Understanding these kinases and their role in cancer can aid in developing precision medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)