Nuclear Transport Signals Control Cellular Localization and Function of Androgen Receptor Cofactor p44/WDR77
2011

How p44/WDR77 Controls Androgen Receptor Function in Prostate Cancer

publication Evidence: moderate

Author Information

Author(s): Gu Zhongping, Zhou Liran, Gao Shen, Wang Zhengxin

Primary Institution: The University of Texas MD Anderson Cancer Center

Hypothesis

The study investigates the nuclear transport signals that control the localization and function of the androgen receptor cofactor p44/WDR77 in prostate cancer cells.

Conclusion

The study found that p44/WDR77's nuclear localization is essential for its function as a transcriptional cofactor for the androgen receptor, and this localization is disrupted in AR-positive prostate cancer cells.

Supporting Evidence

  • p44/WDR77 localizes in the cytoplasm during early prostate development and in the nucleus in adult prostate.
  • Nuclear localization of p44/WDR77 is essential for its function as a transcriptional cofactor for the androgen receptor.
  • In AR-positive prostate cancer cells, the nuclear localization signals of p44/WDR77 are not functional, leading to its cytoplasmic accumulation.

Takeaway

This study shows that a protein called p44/WDR77 needs to be in the nucleus to help control how genes are turned on in prostate cells, but in some cancer cells, it gets stuck in the cytoplasm and can't do its job.

Methodology

The study used mouse prostate and human prostate cancer cells to investigate the subcellular localization of p44/WDR77 and its nuclear transport signals through various assays including immunostaining and mutagenesis.

Limitations

The study primarily focuses on specific prostate cancer cell lines and may not fully represent all prostate cancer types.

Digital Object Identifier (DOI)

10.1371/journal.pone.0022395

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