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Protein kinase D1 inhibition interferes with mitosis progression
Author(s) -
Martínez-León Eduardo,
Amable Gastón,
Jácamo Rodrigo,
Picco María Elisa,
Anaya Laura,
Rozengurt Enrique,
Rey Osvaldo
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28651
Subject(s) - mitosis , microbiology and biotechnology , anaphase , biology , pkd1 , interphase , metaphase , cell division , mitotic exit , cell cycle , polo like kinase , cell , genetics , chromosome , gene , polycystic kidney disease , kidney
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.