TY - JOUR
T1 - Protein kinase D1 inhibition interferes with mitosis progression
AU - Martínez-León, Eduardo
AU - Amable, Gastón
AU - Jácamo, Rodrigo
AU - Picco, María Elisa
AU - Anaya, Laura
AU - Rozengurt, Enrique
AU - Rey, Osvaldo
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/11
Y1 - 2019/11
N2 - Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD-specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142-70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.
AB - Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD-specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142-70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.
KW - PKD1
KW - cancer
KW - mitosis
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U2 - 10.1002/jcp.28651
DO - 10.1002/jcp.28651
M3 - Article
C2 - 30997696
AN - SCOPUS:85069695703
SN - 0021-9541
VL - 234
SP - 20510
EP - 20519
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 11
ER -