hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci

Sharma, Manju; Li, Xiaoyü; Wang, Yuzhuo; Zarnegar, Mark A.; Huang, Chun‐Yin; Palvimo, Jorma J.; Lim, Bing; Sun, Zijie

doi:10.1093/emboj/cdg585

Cited by 115 publications

(161 citation statements)

References 62 publications

Supporting

Mentioning

150

Contrasting

Order By: Relevance

“…Intriguingly, AR also demonstrates a downregulation or degradation pattern during mitosis in androgen-sensitive prostate cancer cells (Litvinov et al, 2006). Besides its well-characterized roles in regulation of prostatic cell growth and differentiation via regulation of its target genes, AR is also shown to play a novel role in DNA replication in prostate cancer cells via a mechanism of forming pre-replicative complexes with some transcriptional co-regulatory proteins at DNA replication foci and such complexes become degraded during mitosis by a proteasome-dependent pathway, thus restricting only one round of DNA replication per cell cycle (Sharma et al, 2003;Huang et al, 2005). On the basis of the analogous degradation expression pattern shown by AR during cell-cycle progression, we speculate that ERRb may also perform similar function as a licensing factor for DNA replication in proliferating prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Orphan nuclear receptor estrogen-related receptor-β suppresses in vitro and in vivo growth of prostate cancer cells via p21WAF1/CIP1 induction and as a potential therapeutic target in prostate cancer

Wong

Wang

et al. 2007

Oncogene

View full text Add to dashboard Cite

Recent studies indicate that estrogen-related receptors (ERRs) are involved in similar estrogen receptor (ER) regulatory pathways and play roles in energy and lipid metabolism. Here, we analysed the functional role of ERRb in prostate cancer cell growth regulation in an androgen-sensitive and androgen-insensitive prostate cancer cell lines. ERRb was expressed in normal human prostates, but exhibited a reduced expression in prostate cancer lesions. Stable ERRb expression suppressed significantly cell proliferation and tumorigenicity of LNCaP and DU145 cells, accompanied by an S-phase suppression and increased p21 expression. Reporter and chromatin immunoprecipitation assays showed that ERRb could directly transactivate p21 gene promoter, which could be further enhanced by peroxisome proliferatoractivated receptor-c coactivator-1a. Truncation analysis showed that ERRb-mediated p21 transactivation and prostate cancer cell growth inhibition required intact DNA-binding domain and AF2 domains in ERRb. Interestingly, ERRb displayed a cell cycle associated downregulated expression pattern in ERRb-transduced and non-transduced cells. Finally, we showed that ERRbmediated growth inhibition could be potentiated by an ERRb/c agonist DY131. Knockdown of ERRb by RNA interference could reduce the DY131-induced growth inhibition in prostate cancer cells. Taken together, our findings indicate that ERRb performs a tumor suppressing function in prostate cancer cells, and targeting ERRb could be a potential therapeutic strategy for prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Orphan nuclear receptor estrogen-related receptor-β suppresses in vitro and in vivo growth of prostate cancer cells via p21WAF1/CIP1 induction and as a potential therapeutic target in prostate cancer

Wong

Wang

et al. 2007

Oncogene

View full text Add to dashboard Cite

show abstract

“…Total RNA samples were isolated from E13.5 whole mouse embryos and used for poly(A) RNA purification. Northern blot analysis was carried out as described previously (17). Briefly, 1.5 g of poly(A) RNA samples were electrophoresed on 1% formalin-denatured agarose gel, blotted onto nylon membrane, and then hybridized with a DNA fragment spanning the junction region between exon 4 and exon 5.…”

Section: Methodsmentioning

confidence: 99%

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

Peng

Clark

Luong

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The LZTS2 is a novel ␤-catenin-interacting protein, and its role in development and tumorigenesis is unknown. Results: Lzts2 KO mice show severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis. Conclusion: LZTS2 plays a critical role in kidney and urinary tract development. Significance: A novel mechanism by which LZTS2 regulates ␤-catenin mediated nephrogenesis is implicated.

show abstract

“…PIAS1 and PIAS3 were originally shown to interact with STAT1 and STAT3, respectively, and inhibit their functions (25,26). Recently other PIAS proteins have been shown to function as coregulators for nuclear receptors (27)(28)(29)(30)(31)(32). The first demonstration of a mammalian PIAS protein as a SUMO E3 ligase was shown in the involvement of PIAS1 in p53 sumoylation (33).…”

mentioning

confidence: 99%

Regulation of Smad4 Sumoylation and Transforming Growth Factor-β Signaling by Protein Inhibitor of Activated STAT1

Liang

Melchior

Feng

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The tumor suppressor, Smad4/DPC4, is a common signal transducer in transforming growth factor-␤ (TGF-␤) signaling. In this study, we demonstrated that the protein inhibitor of activated STAT1 (PIAS1) regulates the signaling potential of Smad4 through a sumoylation-dependent mechanism. PIAS1 was shown to be an E3 ligase for Smad4 sumoylation in vitro and in vivo. The ubiquitin/proteasome pathway controls the turnover of products of many oncogenes and tumor suppressor genes and thus plays a major role in cancer development (1-5). Recently, a number of ubiquitin-related proteins have also been found in eukaryotic cells. These proteins, including the small ubiquitinlike modifier 1 (SUMO1), 1 utilize a conjugation system that is similar to ubiquitination (6, 7). In particular, SUMO is activated in an ATP-dependent manner by an E1 enzyme consisting of the Aos1/Uba2 heterodimer and then transferred to the SUMO-conjugating E2 enzyme Ubc9 and subsequently ligated to the substrate. In contrast to ubiquitination, SUMO1 modifications of target proteins do not promote their degradation. Furthermore, SUMO1 modification reduces ubiquitination of tumor suppressor Smad4 (8) and may also preclude ubiquitination of I B (9). The functional consequences of SUMO1 modification vary depending on the target. For example, SUMO1 conjugation is necessary for RanGAP1 localization to the nuclear pore complex (10, 11), for nuclear import of the transcription corepressor CtBP (12), and for localization of promyelocytic leukemia to the nuclear bodies (13). For many other proteins, their covalent modifications by SUMO1 modulate their biological activities (7, 14 -19).Substrates of SUMO conjugation often contain a tetrapeptide motif, i.e. KX(D/E) (where is hydrophobic and X is any amino acid). Structural analysis of the complex between Ubc9 and its substrate, RanGAP1, demonstrates clearly how the motif is specifically recognized by Ubc9 and elucidates nicely why RanGAP1 sumoylation may not depend on an E3 ligase (20). However, more recent reports support the presence of E3 enzymes for sumoylation (21-24). In particular, a family of SUMO E3 ligases, termed protein inhibitors of activated STAT (PIAS), has recently been discovered (21,22). The PIAS protein family consists of five members: PIAS1, PIAS3, PIASx␣, PIASx␤, and PIASy. PIAS1 and PIAS3 were originally shown to interact with STAT1 and STAT3, respectively, and inhibit their functions (25,26). Recently other PIAS proteins have been shown to function as coregulators for nuclear receptors (27-32). The first demonstration of a mammalian PIAS protein as a SUMO E3 ligase was shown in the involvement of PIAS1 in p53 sumoylation (33). PIAS proteins resemble the RING-class ubiquitin E3 ligases and bind to Ubc9 through the RING finger domain (34). The RING finger domain is highly conserved among PIAS proteins and is supported by the observation that, similar to PIAS1, PIASx␤ also promotes the sumoylation of CtBP (12), p53, and c-Jun (35). Although PIASx␣ binds to the androgen receptor through the RING ...

show abstract

hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci

Cited by 115 publications

References 62 publications

Orphan nuclear receptor estrogen-related receptor-β suppresses in vitro and in vivo growth of prostate cancer cells via p21WAF1/CIP1 induction and as a potential therapeutic target in prostate cancer

Orphan nuclear receptor estrogen-related receptor-β suppresses in vitro and in vivo growth of prostate cancer cells via p21WAF1/CIP1 induction and as a potential therapeutic target in prostate cancer

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

Regulation of Smad4 Sumoylation and Transforming Growth Factor-β Signaling by Protein Inhibitor of Activated STAT1

Contact Info

Product

Resources

About