Cervone, Nando
(2017)
Evidence that Maintenance and Resolution of the
Spindle Assembly Checkpoint does not require
Activity of Protein Phosphatase 2A.
[Tesi di dottorato]
Item Type: |
Tesi di dottorato
|
Resource language: |
English |
Title: |
Evidence that Maintenance and Resolution of the
Spindle Assembly Checkpoint does not require
Activity of Protein Phosphatase 2A. |
Creators: |
Creators | Email |
---|
Cervone, Nando | cervone.nando@gmail.com |
|
Date: |
6 April 2017 |
Number of Pages: |
51 |
Institution: |
Università degli Studi di Napoli Federico II |
Department: |
Medicina Molecolare e Biotecnologie Mediche |
Dottorato: |
Medicina molecolare e biotecnologie mediche |
Ciclo di dottorato: |
29 |
Coordinatore del Corso di dottorato: |
nome | email |
---|
Avvedimento, Vittorio Enrico | UNSPECIFIED |
|
Tutor: |
nome | email |
---|
Grieco, Domenico | UNSPECIFIED |
|
Date: |
6 April 2017 |
Number of Pages: |
51 |
Keywords: |
PP2A, Spindle assembly checkpoint |
Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
Date Deposited: |
03 May 2017 08:47 |
Last Modified: |
16 Mar 2018 13:09 |
URI: |
http://www.fedoa.unina.it/id/eprint/11553 |
DOI: |
10.6093/UNINA/FEDOA/11553 |

Collection description
Mitosis is the critical stage of the cell cycle deputed to form two daughter cells by
the faithful separation of replicated chromosomes of a mother cell into two
identical sets, daughter cells genomes. Inappropriate resolution of sister
chromatids, prior to proper bipolar attachments, during mitosis, leads to random
chromosomes segregation and aneuploidy, a deleterious condition often associated
with various pathological conditions (Weaver & Cleveland, 2006). To prevent
errors in chromosome segregation, a safeguard pathway, the spindle assembly
checkpoint (SAC), is activated by improper kinetochore-spindle microtubule
attachments and prevents activation of the mitosis exit-promoting ubiquitin-ligase
Anaphase Promoting Complex/Cyclosome (APC/C) to delay mitosis exit until all
the chromosomes become correctly bi-orientated at the equator of the metaphase
plate (Lampson et al., 2004).
Several protein kinases and phosphatases play essential roles in these processes
presumably by controlling the phosphorylation status of a number of proteins
involved in SAC control. There is a balance between kinase and phosphatase
activities and this balance is constantly changing during the time required for
spindle assembly completion (Visconti et al., 2013).
Protein phosphatases as protein phosphatase 1 (PP1) and protein phosphatase 2A
(PP2A), are well known to be required for mitosis completion, however, whether
and how activity of these phosphatases is involved in SAC control is still
incompletely understood.
PP2A, in particular, is a holoenzyme composed by a scaffolding (A), a catalytic
(C) and a regulatory (B) subunit. The B subunit consists of four distinct
subfamilies (B, B’, B” and B”’) acting as target modulators to provide substrate
specificity; holoenzyme formation, in all its three subunits, is fundamental for
PP2A action (Wurzenberger & Gerlich, 2011; Rogers et al., 2016).
PP2A has been suggested to contribute to SAC resolution and to the metaphaseto-
anaphase transition, namely through experiments based on small interfering
6
RNAs-mediated genetic knockdown of the various PP2A subunits (Schmitz et al.,
2010; Wurzenberger & Gerlich, 2011; Kruse et al., 2013; Nijlenhuis et al., 2014).
However, the contribution of the catalytic activity of PP2A in SAC control has not
been directly investigated.
In this work we investigated the role of PP2A activity in SAC regulation by using
inhibitors of PP2A catalytic activity, like Okadaic acid (OA) and LB 100, without
interfering with holoenzyme formation. We found compelling evidence that the
catalytic activity of PP2A does not substantially affect SAC maintenance or
resolution in human cells.
Downloads per month over past year
Actions (login required)
 |
View Item |