Male germ cell-associated kinase is overexpressed in prostate cancer cells and causes mitotic defects via deregulation of APC/C CDH1

L. Y. Wang, Hsing-Jien Kung

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Male germ cell-associated kinase (MAK), a direct transcriptional target of androgen receptor (AR), is a co-activator of AR. In this study, we determined the activating mechanism of MAK and identified a previously unknown AR-independent role of MAK in mitosis. We found that MAK kinase activity requires dual phosphorylation of the conserved TDY motif and that the phosphorylation is dynamic during cell cycle. MAK associates with CDH1 (FZR1, fizzy/cell division cycle 20 related 1) and phosphorylates CDH1 at sites phosphorylated by cyclin-dependent kinases. When MAK is overexpressed, the binding of CDH1 to anaphase promoting complex/cyclosome decreased, resulting in an attenuation of anaphase-promoting complex/C ubiquitin ligase activity and the consequential stabilization of the CDH1 targets such as Aurora kinase A and Polo-like kinase 1. As such, overexpression of MAK leads to mitotic defects such as centrosome amplification and lagging chromosomes. Our immunohistochemistry result showed that MAK is overexpressed in prostate tumor tissues, suggesting a role of MAK in prostate carcinogenesis. Taken with our previous results, our data implicate MAK in both AR activation and chromosomal instability, acting in both early and late prostate cancer development.

Original languageEnglish (US)
Pages (from-to)2907-2918
Number of pages12
JournalOncogene
Volume31
Issue number24
DOIs
StatePublished - Jun 14 2012

Fingerprint

Androgen Receptors
Germ Cells
Prostatic Neoplasms
Phosphotransferases
Anaphase-Promoting Complex-Cyclosome
Cdh1 Proteins
Prostate
Ubiquitin C
Aurora Kinase A
Phosphorylation
Centrosome
Chromosomal Instability
Cyclin-Dependent Kinases
Ligases
Mitosis
Cell Cycle
Carcinogenesis
Chromosomes
Immunohistochemistry
Neoplasms

Keywords

  • APC/C complex
  • CDH1/FZR1
  • MAK
  • mitosis
  • prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Male germ cell-associated kinase is overexpressed in prostate cancer cells and causes mitotic defects via deregulation of APC/C CDH1 . / Wang, L. Y.; Kung, Hsing-Jien.

In: Oncogene, Vol. 31, No. 24, 14.06.2012, p. 2907-2918.

Research output: Contribution to journalArticle

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