The human RNA polymerase II-associated factor (hPAF) complex is comprised of five subunits that include hPaf1, parafibromin, hLeo1, hCtr9 and hSki8. This multifaceted complex was first identified in yeast (yPAF) and subsequently in Drosophila and humans. Recent advances in the study on hPAF have revealed various functions of the complex in humans that are similar to yPAF, including efficient transcription elongation, mRNA quality control and cell cycle regulation. A major component of the hPAF complex, hPaf1, is amplified and overexpressed in pancreatic cancer. The parafibromin subunit of the hPAF complex is a product of the hereditary hyperparathyroidism type 2 (HRPT-2) tumor-suppressor gene, which is mutated in the germ line of hyperparathyroidism-jaw tumor patients. This review evaluates the role of the hPAF complex and its individual subunits in endocrine and pancreatic cancers. It focuses on the functions of the hPAF complex and its individual subunits and dysregulation of the complex, thus providing an insight into its potential involvement in the development of endocrine cancers and other tumor types.
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http://dx.doi.org/10.1586/17446651.3.5.557 | DOI Listing |
Eur J Med Chem
September 2023
Drug Discovery and Development Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai, 201210, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; Lingang Laboratory, Shanghai, 200031, China. Electronic address:
Betulinic acid (BA) is a natural pentacyclic triterpenoid that has a wide range of biological and pharmacological effects. Here, computational methods such as pharmacophore screening and reverse docking were used to predict the potential target for BA. Retinoic acid receptor-related orphan receptor gamma (RORγ) was confirmed as its target by several molecular assays as well as crystal complex structure determination.
View Article and Find Full Text PDFCancers (Basel)
February 2021
Department of Pathology and Microbiology, Nebraska Medical Center, Omaha, NE 68198, USA.
The Plexins family of proteins are well-characterized transmembrane receptors of semaphorins, axon guidance cue molecules, that mediate the cell attraction or repelling effects for such cues. Plexins and their ligands are involved in numerous cellular activities, such as motility, invasion, and adhesion to the basement membrane. The detachment of cells and the gain in motility and invasion are hallmarks of the cancer metastasis cascade, thus generating interest in exploring the role of plexins in cancer metastasis.
View Article and Find Full Text PDFPharmaceutics
March 2020
Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA.
BMC Cancer
June 2019
Department of Hepato-Pancreato-Biliary Surgery, Institute of Clinical Medicine, University of Oslo, PO Box 1171, Blindern, 0318, Oslo, Norway.
Background: Gemcitabine remains a cornerstone in chemotherapy of pancreatic ductal adenocarcinoma (PDAC) despite suboptimal clinical effects that are partly due to the development of chemoresistance. Pancreatic stellate cells (PSCs) of the tumor stroma are known to interact with pancreatic cancer cells (PCCs) and influence the progression of PDAC through a complex network of signaling molecules that involve extracellular matrix (ECM) proteins. To understand tumor-stroma interactions regulating chemosensitivity, the role of PSC-secreted fibronectin (FN) in the development of gemcitabine resistance in PDAC was examined.
View Article and Find Full Text PDFBMC Cancer
March 2019
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Background: Despite its relatively low incidence, pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths because of the aggressive growth/metastasis of the tumor, the lack of early symptoms, and the poor treatment options. Basic research to identify potential therapeutic targets for PDAC is greatly needed.
Methods: We used a negative-selection genome-wide CRISPR screen to identify essential genes in the PANC-1 human pancreatic carcinoma cell line.
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