Identification of Myb-binding protein 1A (MYBBP1A) as a novel substrate for aurora B kinase.
Aurora kinases are mitotic enzymes involved in centrosome maturation and separation, spindle assembly and stability, and chromosome condensation, segregation, and cytokinesis and represent well known targets for cancer therapy because their deregulation has been linked to tumorigenesis. The availability of suitable markers is of crucial importance to investigate the functions of Auroras and monitor kinase inhibition in in vivo models and in clinical trials. Extending the knowledge on Aurora substrates could help to better understand their biology and could be a source for clinical biomarkers. Using biochemical, mass spectrometric, and cellular approaches, we identified MYBBP1A as a novel Aurora B substrate and serine 1303 as the major phosphorylation site. MYBBP1A is phosphorylated in nocodazole-arrested cells and is dephosphorylated upon Aurora B silencing or by treatment with Danusertib, a small molecule inhibitor of Aurora kinases. Furthermore, we show that MYBBP1A depletion by RNA interference causes mitotic progression delay and spindle assembly defects. MYBBP1A has until now been described as a nucleolar protein, mainly involved in transcriptional regulation. The results presented herein show MYBBP1A as a novel Aurora B kinase substrate and reveal a not yet recognized link of this nucleolar protein to mitosis.
Perrera
Claudia
C
Nerviano Medical Sciences, Nerviano 20014 MI, Italy. Claudia.Perrera@nervianoms.com
Colombo
Riccardo
R
Valsasina
Barbara
B
Carpinelli
Patrizia
P
Troiani
Sonia
S
Modugno
Michele
M
Gianellini
Laura
L
Cappella
Paolo
P
Isacchi
Antonella
A
Moll
Jurgen
J
Rusconi
Luisa
L
D000595:Amino Acid Sequence; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013379:Substrate Specificity; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D047428:Protein Kinase Inhibitors; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D012694:Serine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases