Plk5, a Polo Box Domain-Only Protein with Specific Roles in Neuron Differentiation and Glioblastoma Suppression

被引:104
作者
de Carcer, Guillermo [1 ,2 ]
Escobar, Beatriz [1 ,2 ]
Higuero, Alonso M. [3 ]
Garcia, Laura [1 ,2 ]
Anson, Alejandra [1 ,2 ]
Perez, Gema [4 ]
Mollejo, Manuela [4 ]
Manning, Gerard [5 ]
Melendez, Barbara [4 ]
Abad-Rodriguez, Jose [3 ]
Malumbres, Marcos [1 ,2 ]
机构
[1] Ctr Nacl Invest Oncol, Cell Div, E-28029 Madrid, Spain
[2] Ctr Nacl Invest Oncol, Canc Grp, E-28029 Madrid, Spain
[3] Hosp Nacl Paraplejicos, Membrane Biol & Axonal Repair Lab, Toledo, Spain
[4] Hosp Virgen Salud, Unidad Invest Patol Mol, Toledo, Spain
[5] Salk Inst Biol Studies, Razavi Newman Ctr Bioinformat, La Jolla, CA USA
关键词
CELL-CYCLE KINASES; CENTRIOLE DUPLICATION; DNA-DAMAGE; PHEOCHROMOCYTOMA CELLS; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; MAMMALIAN-CELLS; INK4; INHIBITORS; NERVOUS-SYSTEM; CANCER-THERAPY;
D O I
10.1128/MCB.00607-10
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1225 / 1239
页数:15
相关论文
共 64 条
[1]  
Alberts GF, 2004, CELL CYCLE, V3, P678
[2]   The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus [J].
Andrysik, Zdenek ;
Bernstein, William Z. ;
Deng, Li ;
Myer, David L. ;
Li, Ya-Qin ;
Tischfield, Jay A. ;
Stambrook, Peter J. ;
Bahassi, El Mustapha .
NUCLEIC ACIDS RESEARCH, 2010, 38 (09) :2931-2943
[3]   Regulation of Postsynaptic RapGAP SPAR by Polo-like Kinase 2 and the SCFβ-TRCP Ubiquitin Ligase in Hippocampal Neurons [J].
Ang, Xiaolu L. ;
Seeburg, Daniel P. ;
Sheng, Morgan ;
Harper, J. Wade .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (43) :29424-29432
[4]   Polo-like kinases: conservation and divergence in their functions and regulation [J].
Archambault, Vincent ;
Glover, David M. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (04) :265-275
[5]   Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation [J].
Bahassi, ELM ;
Hennigan, RF ;
Myer, DL ;
Stambrook, PJ .
ONCOGENE, 2004, 23 (15) :2658-2663
[6]   Mammalian Polo-like kinase 3 (PIU) is a multifunctional protein involved in stress response pathways [J].
Bahassi, EM ;
Conn, CW ;
Myer, DL ;
Hennigan, RF ;
McGowan, CH ;
Sanchez, Y ;
Stambrook, PJ .
ONCOGENE, 2002, 21 (43) :6633-6640
[7]  
Banker G., 1998, CULTURING NERVE CELL
[8]   Polo-like kinases and the orchestration of cell division [J].
Barr, FA ;
Silljé, HHW ;
Nigg, EA .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (06) :429-440
[9]   SAK/PLK4 is required for centriole duplication and flagella development [J].
Bettencourt-Dias, M ;
Rodrigues-Martins, A ;
Carpenter, L ;
Riparbelli, M ;
Lehmann, L ;
Gatt, MK ;
Carmo, N ;
Balloux, F ;
Callaini, G ;
Glover, DM .
CURRENT BIOLOGY, 2005, 15 (24) :2199-2207
[10]   The sea urchin kinoine: A first look [J].
Bradham, Cynthia A. ;
Foltz, Kathy R. ;
Beane, Wendy S. ;
Arnone, Maria I. ;
Rizzo, Francesca ;
Coffman, James A. ;
Mushegian, Arcady ;
Goel, Manisha ;
Morales, Julia ;
Geneviere, Anne-Marie ;
Lapraz, Francois ;
Robertson, Anthony J. ;
Kelkar, Femant ;
Loza-Coll, Mariano ;
Townley, Ian K. ;
Raisch, Michael ;
Roux, Michelle M. ;
Lepage, Thierry ;
Gache, Christian ;
McClay, David R. ;
Manning, Gerard .
DEVELOPMENTAL BIOLOGY, 2006, 300 (01) :180-193