Dataset Information

Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

ABSTRACT: The androgen receptor (AR) cofactor p44/WDR77, which regulates expression of a set of androgen target genes, is required for differentiation of prostate epithelium. Aberrant localization of p44/WDR77 in the cytoplasm is associated with prostate tumorigenesis. Here, we describe studies that used the mouse prostate and human prostate cancer cells as model systems to investigate signals that control subcellular localization of p44/WDR77. We observed distinct subcellular location of p44/WDR77 during prostate development. p44/WDR77 localizes in the cytoplasm at the early stage of prostate development, when prostate epithelial cells are rapidly proliferating, and in the nucleus in adult prostate, when epithelial cells are fully differentiated. Subcellular localization assays designed to span the entire open-reading frame of p44/WDR77 protein revealed the presence of two nuclear exclusion signal (NES) and three nuclear localization signal (NLS) sequences in the p44/WDR77 protein. Site-directed mutagenesis of critical residues within an NLS led to loss of nuclear localization and transcriptional activity of p44/WDR77, suggesting that nuclear localization of p44/WDR77 is essential for its function as a transcriptional cofactor for AR. Three identified NLS were not functional in AR-positive prostate cancer (LNCaP and 22RV1) cells, which led to localization of p44/WDR77 in cytoplasm. The function of NLS in LNCaP cells could be restored by factor(s) from Cos 7 or PC3 cells. Mass spectrometric (MALDI-TOF/TOF) analysis identified proteins associated with an NLS and an NES in prostate cancer cells. These results provide a basis for understanding subcellular transport of p44/WDR77 during prostate development and tumorigenesis.

SUBMITTER: Gu Z

PROVIDER: S-EPMC3137635 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

Gu Zhongping Z Zhou Liran L Gao Shen S Wang Zhengxin Z

PloS one 20110715 7

The androgen receptor (AR) cofactor p44/WDR77, which regulates expression of a set of androgen target genes, is required for differentiation of prostate epithelium. Aberrant localization of p44/WDR77 in the cytoplasm is associated with prostate tumorigenesis. Here, we describe studies that used the mouse prostate and human prostate cancer cells as model systems to investigate signals that control subcellular localization of p44/WDR77. We observed distinct subcellular location of p44/WDR77 during ...[more]

PMID: 21789256

Similar Datasets

Project description:Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. Importance: Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid protein (VP1) of porcine parvovirus. The major protein (VP2) nuclear localization was shown to depend on a complex structural motif. This motif can be used as a strategy by the virus to avoid transport of incorrectly folded proteins and to selectively import assembled trimers into the nucleus. Structural nuclear localization motifs can also be important for nuclear proteins without a classic basic amino acid stretch, including multimeric cellular proteins.

Dataset Information

Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

Publications

Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets