RACK1 affects the progress of G2/M by regulating Aurora-A

Suqin Shen; Huan Feng; Yichen Le; Jun Ni; Long Yu; Jiaxue Wu; Meirong Bai

doi:10.1080/15384101.2019.1642065

RACK1 affects the progress of G2/M by regulating Aurora-A

Cell Cycle. 2019 Sep;18(18):2228-2238. doi: 10.1080/15384101.2019.1642065. Epub 2019 Jul 29.

Authors

Suqin Shen¹, Huan Feng¹, Yichen Le¹, Jun Ni², Long Yu¹, Jiaxue Wu¹, Meirong Bai^{1

3}

Affiliations

¹ State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University , Shanghai , P. R. China.
² Department Oncology, Hutchison Medi Pharma , Shanghai , China.
³ Cardiovascular Research Institute and Department of Physiology, University of California San Francisco , San Francisco , CA , USA.

Abstract

Aurora-A is a serine/threonine kinase, which is overexpressed in multiple human cancers and plays a key role in tumorigenesis and tumor development. In this study, we found that the receptor of activated C-kinase1 (RACK1), an important regulator of biological functions, interacted with Aurora-A and co-localized with Aurora-A at centrosomes. Moreover, RACK1 induces the auto-phosphorylation of Aurora-A in vitro and in vivo. Depletion of RACK1 impaired the activation of Aurora-A in late G2 phase, then inhibited the mitotic entry and leaded to multi-polarity, severe chromosome alignment defects, or centrosome amplification. Taken together, these results suggest that RACK1 is a new partner of Aurora-A and play a critical role in the regulation of the Aurora-A activity during mitosis, which may provide a basis for future anticancer studies targeting Aurora-A.

Keywords: Aurora-A; G2/M; Mitosis; Phosphorylation; RACK1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aurora Kinase A / chemistry
Aurora Kinase A / genetics
Aurora Kinase A / metabolism*
Catalytic Domain
Centrosome / metabolism
G2 Phase Cell Cycle Checkpoints / genetics*
HeLa Cells
Humans
M Phase Cell Cycle Checkpoints / genetics*
Neoplasm Proteins / chemistry
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Phosphorylation / genetics
Protein Binding
Protein Stability
Receptors for Activated C Kinase / chemistry
Receptors for Activated C Kinase / genetics
Receptors for Activated C Kinase / metabolism*
Signal Transduction / genetics
Spindle Apparatus / metabolism
Transfection

Substances

Neoplasm Proteins
RACK1 protein, human
Receptors for Activated C Kinase
AURKA protein, human
Aurora Kinase A

Grants and funding

This work was supported by National Nature Science Foundation of China (81702742 to S.S.), National Nature Science Foundation of China (81272250 and 81472619 to J.W.)