Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524.

Anna P Baron | Conrad von Schubert | Fabien Cubizolles | Gerhard Siemeister | Marion Hitchcock | Anne Mengel | Jens Schröder | Amaury Fernández-Montalván | Franz von Nussbaum | Dominik Mumberg | Erich A Nigg
eLife | 2016

The kinase Bub1 functions in the spindle assembly checkpoint (SAC) and in chromosome congression, but the role of its catalytic activity remains controversial. Here, we use two novel Bub1 inhibitors, BAY-320 and BAY-524, to demonstrate potent Bub1 kinase inhibition both in vitro and in intact cells. Then, we compared the cellular phenotypes of Bub1 kinase inhibition in HeLa and RPE1 cells with those of protein depletion, indicative of catalytic or scaffolding functions, respectively. Bub1 inhibition affected chromosome association of Shugoshin and the chromosomal passenger complex (CPC), without abolishing global Aurora B function. Consequently, inhibition of Bub1 kinase impaired chromosome arm resolution but exerted only minor effects on mitotic progression or SAC function. Importantly, BAY-320 and BAY-524 treatment sensitized cells to low doses of Paclitaxel, impairing both chromosome segregation and cell proliferation. These findings are relevant to our understanding of Bub1 kinase function and the prospects of targeting Bub1 for therapeutic applications.

Pubmed ID: 26885717

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


MetaMorph Microscopy Automation and Image Analysis Software (tool)

RRID:SCR_002368

Software tool for automated microscope acquisition, device control, and image analysis. Used for integrating dissimilar fluorescent microscope hardware and peripherals into a single custom workstation, while providing all the tools needed to perform analysis of acquired images. Offers user friendly application modules for analysis such as cell signaling, cell counting, and protein expression.

View all literature mentions

Bethyl (tool)

RRID:SCR_013554

An Antibody supplier

View all literature mentions

SlideBook (tool)

RRID:SCR_014300

Digital microscopy software for research microscopy. It comes standard with drivers to control numerous instruments in and around the microscope. When online, data is acquired in a native-3D format over time, color and specimen locations in customizable experiment protocols. Data can be analyzed by a wide variety of tools for image processing including mathematical operations, statistics functions, analysis scripting and import to/export from MATLAB. Additional modules are available for special applications ranging from deconvolution to photomanipulation to multiphoton.

View all literature mentions

NCI-H1299 (tool)

RRID:CVCL_0060

Cell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HeLa (tool)

RRID:CVCL_0030

Cell line HeLa is a Cancer cell line with a species of origin Homo sapiens

View all literature mentions

HeLa S3 (tool)

RRID:CVCL_0058

Cell line HeLa S3 is a Cancer cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions