PIM activity in tumours: A key node of therapy resistance
Publication date: Available online 22 October 2017 Source:Advances in Biological Regulation Author(s): Richard J. Rebello, Alisée V. Huglo, Luc Furic The PIM kinases are proto-oncogenes which have been shown to facilitate cell survival and proliferation to drive malignancy and resistance post-therapy. They are able to suppress cell death signals, sustain PI3K/AKT/mTORC1 pathway activity and regulate the MYC oncogenic program. Recent work has revealed PIM kinase essentiality for advanced tumour maintenance and described tumour sensitivity to small molecule inhibitors targeting PIM kinase in multiple malignancies. (Sou...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Review of four major distinct types of human phospholipase A2
Publication date: Available online 23 October 2017 Source:Advances in Biological Regulation Author(s): Alexis M. Vasquez, Varnavas D. Mouchlis, Edward A. Dennis The phospholipase A2 superfamily of enzymes plays a significant role in the development and progression of numerous inflammatory diseases. Through their catalytic action on membrane phospholipids, phospholipases are the upstream regulators of the eicosanoid pathway releasing free fatty acids for cyclooxygenases, lipoxygenases, and cytochrome P450 enzymes which produce various well-known inflammatory mediators including leukotrienes, thromboxanes and prostaglan...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Nuclear inositide signaling and cell cycle
Publication date: Available online 23 October 2017 Source:Advances in Biological Regulation Author(s): Stefano Ratti, Giulia Ramazzotti, Irene Faenza, Roberta Fiume, Sara Mongiorgi, Anna Maria Billi, James A. McCubrey, Pann-Ghill Suh, Lucia Manzoli, Lucio Cocco, Matilde Y. Follo Phosphatidylinositols (PIs) are responsible for several signaling pathways related to many cellular functions, such as cell cycle regulation at different check-points, cell proliferation, cell differentiation, membrane trafficking and gene expression. PI metabolism is not only present at the cytoplasmic level, but also at the nuclear o...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions
Publication date: Available online 27 October 2017 Source:Advances in Biological Regulation Author(s): Junaid Kashir, Michail Nomikos, F. Anthony Lai Oocyte activation is a fundamental event at mammalian fertilisation, initiated by a series of characteristic calcium (Ca2+) oscillations in mammals. This characteristic pattern of Ca2+ release is induced in a species-specific manner by a sperm-specific enzyme termed phospholipase C zeta (PLCζ). Reduction or absence of functional PLCζ within sperm underlies male factor infertility in humans, due to mutational inactivation or abrogation of PLCζ protein expression. Under...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Dysregulation of mRNA translation and energy metabolism in cancer
Publication date: Available online 2 November 2017 Source:Advances in Biological Regulation Author(s): Matthew Leibovitch, Ivan Topisirovic Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
PLC γ1: Potential arbitrator of cancer progression
Publication date: Available online 8 November 2017 Source:Advances in Biological Regulation Author(s): Hyun-Jun Jang, Pann-Ghill Suh, Yu Jin Lee, Kyeong Jin Shin, Lucio Cocco, Young Chan Chae Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca2+) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. PLCγ1, one of the primary subtypes of PLC, is direc...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Proliferative and metastatic roles for Phospholipase D in mouse models of cancer
Publication date: Available online 14 November 2017 Source:Advances in Biological Regulation Author(s): Eric Roth, Michael A. Frohman Phospholipase D (PLD) activity has been proposed to facilitate multiple steps in cancer progression including growth, metabolism, angiogenesis, and mobility. The canonical enzymes PLD1 and PLD2 enact their diverse effects through hydrolyzing the membrane lipid phosphatidylcholine to generate the second messenger and signaling lipid phosphatidic acid (PA). However, the widespread expression of PLD1 and PLD2 in normal tissues and the additional distinct enzymatic mechanisms through which P...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Normalization of mass spectrometry data (NOMAD)
Publication date: Available online 20 November 2017 Source:Advances in Biological Regulation Author(s): Carl Murie, Brian Sandri, Ann-Sofi Sandberg, Timothy J. Griffin, Janne Lehtiö, Christine Wendt, Ola Larsson iTRAQ and TMT reagent-based mass spectrometry (MS) are commonly used technologies for quantitative proteomics in biological samples. Such studies are often performed over multiple MS runs, potentially resulting in introduction of MS run bias that could affect downstream analysis. Such MS data have therefore commonly been normalized using a reference sample which is included in each MS run. We show, howeve...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Molecular and cellular mechanisms of chemoresistance in pancreatic cancer
Publication date: Available online 22 November 2017 Source:Advances in Biological Regulation Author(s): Aleksandra Adamska, Omar Elaskalani, Aikaterini Emmanouilidi, Minkyoung Kim, Norbaini Binti Abdol Razak, Pat Metharom, Marco Falasca Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available option...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Forms and functions of store-operated calcium entry mediators, STIM and Orai
Publication date: Available online 22 November 2017 Source:Advances in Biological Regulation Author(s): James W. Putney Calcium signals arise by multiple mechanisms, including mechanisms of release of intracellular stored Ca2+, and the influx of Ca2+ through channels in the plasma membrane. One mechanism that links these two sources of Ca2+ is store-operated Ca2+ entry, the most commonly encountered version of which involves the extensively studied calcium-release-activated Ca2+ (CRAC) channel. The minimal and essential molecular components of the CRAC channel are the STIM proteins that function as Ca2+ sensors in the e...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors
Publication date: December 2017 Source:Advances in Biological Regulation, Volume 66 Author(s): Takao Fujisawa Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an attractive drug target, owing to its essential role in a wide variety of human diseases including neurodegenerative disorders, inflammatory diseases and cancer. Recent studies have suggested that pharmacological manipulations using small molecule ASK1 inhibitors may be beneficial in experimental human disease models. In this review, we highlight the current und...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
ASK family in cardiovascular biology and medicine
Publication date: December 2017 Source:Advances in Biological Regulation, Volume 66 Author(s): Tingting Liu, Huanjiao Jenny Zhou, Wang Min Cardiovascular disease is a major cause of death worldwide. Mitogen-activated protein kinase (MAPK) signal cascades signaling pathways play crucial roles in cardiovascular pathophysiology. Apoptosis signal-regulating kinase (ASK) family members ASK1, ASK2 and ASK3 are the key molecules in MAPK signal cascades and are activated by various stresses. ASK1 is the most extensively studied MAPKKK and is involved in regulation of the cellular functions such as cell survival, proliferation...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Physiological roles of ASK family members in innate immunity and their involvement in pathogenesis of immune diseases
Publication date: December 2017 Source:Advances in Biological Regulation, Volume 66 Author(s): Atsushi Matsuzawa Cells are always exposed to various types of stress, including physical, chemical, and biological stresses, and are required to sense immediately and respond appropriately to these stresses. The apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases, which are activated by not only physicochemical stresses, such as oxidative stress, osmotic pressure, calcium overload, and anti-cancer drugs, but also biological stresses, such as inflammatory cytokines and pathogen infection. Rece...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
ASK family in infection and inflammatory disease
Publication date: December 2017 Source:Advances in Biological Regulation, Volume 66 Author(s): Tomohiko Okazaki Living organisms are continuously exposed to pathogens such as viruses and bacteria. Soon after a limited number of germline-encoded receptors, called pathogen recognition receptors, sense pathogen-associated molecular patterns, hosts trigger innate immune responses, including production of type Ⅰ interferons, proinflammatory cytokines, and cellular apoptosis, to limit propagation of invading pathogens. Importantly, these host responses are also activated during inflammatory diseases, irrespective of pathoge...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
Structural aspects of protein kinase ASK1 regulation
Publication date: December 2017 Source:Advances in Biological Regulation, Volume 66 Author(s): Tomas Obsil, Veronika Obsilova Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK) signaling cascades in response to various stressors. ASK1 activity is tightly regulated through phosphorylation and interaction with various binding partners. However, the mechanistic details underlying the ASK1 regulation are still not fully understood. This revie...
Source: Advances in Biological Regulation - December 16, 2017 Category: Biology Source Type: research
