CONTEXT: p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in responses ranging from apoptosis to cell cycle, induction of expression of cytokine genes, and differentiation. This plethora of activators conveys the complexity of the p38 pathway. This complexity is further complicated by the observation that the downstream effects of p38 MAPK activation may be different depending on types of stimuli, cell types, and various p38 MAPK isoforms involved. OBJECTIVE: This review focuses on the recent advancement of the p38 MAPK isoforms as well as the roles of p38 MAPK in hematologic malignancies. DATA SOURCES: Review of pertinent published literature and work in our laboratory. CONCLUSIONS: In some hematologic malignancies, activation of p38 plays a key role in promoting or inhibiting proliferation and also in increasing resistance to chemotherapeutic agents. The importance of different p38 isoforms in various cellular functions has been acknowledged recently. Further understanding of these isoforms will allow the design of more specific inhibitors to target particular isoforms to maximize the treatment effect and minimize the side effects for treating hematopoietic malignancies.
CONTEXT: p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in responses ranging from apoptosis to cell cycle, induction of expression of cytokine genes, and differentiation. This plethora of activators conveys the complexity of the p38 pathway. This complexity is further complicated by the observation that the downstream effects of p38 MAPK activation may be different depending on types of stimuli, cell types, and various p38 MAPK isoforms involved. OBJECTIVE: This review focuses on the recent advancement of the p38 MAPK isoforms as well as the roles of p38 MAPK in hematologic malignancies. DATA SOURCES: Review of pertinent published literature and work in our laboratory. CONCLUSIONS: In some hematologic malignancies, activation of p38 plays a key role in promoting or inhibiting proliferation and also in increasing resistance to chemotherapeutic agents. The importance of different p38 isoforms in various cellular functions has been acknowledged recently. Further understanding of these isoforms will allow the design of more specific inhibitors to target particular isoforms to maximize the treatment effect and minimize the side effects for treating hematopoietic malignancies.
Authors: Godfrey Grech; Joel Pollacco; Mark Portelli; Keith Sacco; Shawn Baldacchino; Justine Grixti; Christian Saliba Journal: Int J Hematol Date: 2013-12-01 Impact factor: 2.490
Authors: David M Perry; Benjamin Newcomb; Mohamad Adada; Bill X Wu; Patrick Roddy; Kazuyuki Kitatani; Leah Siskind; Lina M Obeid; Yusuf A Hannun Journal: J Biol Chem Date: 2014-06-20 Impact factor: 5.157