Protein kinase D1 inhibition interferes with mitosis progression. Issue 11 (17th April 2019)

• Record Type: Journal Article
• Authors: Martínez-León, Eduardo; Amable, Gastón; Jácamo, Rodrigo; Picco, María Elisa; Anaya, Laura; Rozengurt, Enrique; Rey, Osvaldo
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 11(2019:Nov.)
• Page Start: 20510
• Page End: 20519
• Publication Date: 2019-04-17
• Subjects: cancer -- mitosis -- PKD1; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28651
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: 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. Abstract : Our results show that inhibition of protein kinase D (PKD) activity at the onset of prophase interferes with metaphase progression promoting abnormal mitotic spindle formation, defects in chromosomes alignment, and segregation and apoptosis as well as diminished protein ubiquitination during mitosis suggesting that PKD1 inhibition was associated with spindle assembly checkpoint activation. The obtained results support the hypothesis that PKD1 catalytic activity is associated with mitosis regulation.