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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN Imprimir: 0893-9675
ISSN En Línea: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2014011899
pages 505-516

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

Harrod H. Ling
Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada
Lucia Mendoza-Viveros
Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada
Neel Mehta
Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada
Hai-Ying M. Cheng
Department of Biology, University of Toronto Mississauga, Mississauga, Ontario, Canada

SINOPSIS

In 1984, a cytosolic protein was isolated from bovine brain and coined phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid-binding potential. Its cellular function remained elusive for more than a decade until it was discovered that PEBP had the ability to suppress the Raf1-mitogen activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase inhibitory protein (RKIP). This milestone discovery has paved the way for numerous studies that have now extended the reach of RKIP's function to other signaling cascades, within the context of various physiological and pathophysiological systems. This review will summarize our current knowledge of the neurophysiological roles of RKIP in the mammalian brain, including its function in the circadian clock and synaptic plasticity. It will also discuss evidence for an involvement of RKIP and its derived neuropeptide, hippocampal cholinergic neurostimulating peptide (HCNP), in neural development and differentiation. Implications in certain pathologies such as Alzheimer's disease and brain cancer will be highlighted. By chronicling the diverse functions of RKIP in the brain, we hope that this review will serve as a timely resource that ignites future studies on this versatile, multifaceted protein in the nervous system.


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