Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression.
Polo-like kinases (Plks) are characterized by the presence of a specific domain, known as the polo box (PBD), involved in protein-protein interactions. Plk1 to Plk4 are involved in centrosome biology as well as the regulation of mitosis, cytokinesis, and cell cycle checkpoints in response to genotoxic stress. We have analyzed here the new member of the vertebrate family, Plk5, a protein that lacks the kinase domain in humans. Plk5 does not seem to have a role in cell cycle progression; in fact, it is downregulated in proliferating cells and accumulates in quiescent cells. This protein is mostly expressed in the brain of both mice and humans, and it modulates the formation of neuritic processes upon stimulation of the brain-derived neurotrophic factor (BDNF)/nerve growth factor (NGF)-Ras pathway in neurons. The human PLK5 gene is significantly silenced in astrocytoma and glioblastoma multiforme by promoter hypermethylation, suggesting a tumor suppressor function for this gene. Indeed, overexpression of Plk5 has potent apoptotic effects in these tumor cells. Thus, Plk5 seems to have evolved as a kinase-deficient PBD-containing protein with nervous system-specific functions and tumor suppressor activity in brain cancer.
Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
Guillermo
G
de Cárcer
Beatriz
B
Escobar
Alonso M
AM
Higuero
Laura
L
García
Alejandra
A
Ansón
Gema
G
Pérez
Manuela
M
Mollejo
Gerard
G
Manning
Bárbara
B
Meléndez
José
J
Abad-Rodríguez
Marcos
M
Malumbres
D000818:Animals; D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000166:cytology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D055495:Neurogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D017346:Protein Serine-Threonine Kinases; C549900:polo-like kinase 5, human; C549899:polo-like kinase 5, mouse
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