The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells

Lu, Lifang; Schulz, H.; Wolf, Dieter A

doi:10.1186/1471-2121-3-22

Cited by 71 publications

(27 citation statements)

References 49 publications

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“…It is noteworthy that the molecular mechanism(s) by which Skp2 induces prostate tumor growth has not been fully elucidated. However, multiple signaling pathways, such as phosphatidylinositol 3-kinase (PI3K)/Akt [52], AR [53], PTEN [20], p27 [18], and BRCA2 [54] signaling have been reported to cross-talk with Skp2 in the prostate cancer, and thus it is believed that the cross-talk between Skp2 and these signaling pathways may play critical roles in prostate tumorigenesis. Here, we will discuss the recent advances in our understanding of the role of Skp2 in prostate tumor progression.…”

Section: The Role Of Skp2 In the Development And Progression Of Prmentioning

confidence: 99%

Skp2: A novel potential therapeutic target for prostate cancer

Wang

Gao

Fukushima

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

115

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Prostate cancer is the most frequently diagnosed tumor in men and the second most common cause of cancer-related death for males in the United States. It has been shown that multiple signaling pathways are involved in the pathogenesis of prostate cancer, such as androgen receptor (AR), Akt, Wnt, Hedgehog (Hh) and Notch. Recently, burgeoning amounts of evidence have implicated that the F-box protein Skp2 (S-phase kinase associated protein 2), a well-characterized oncoprotein, also plays a critical role in the development and progression of prostate cancer. Therefore, this review discusses the recent literature regarding the function and regulation of Skp2 in the pathogenesis of prostate cancer. Furthermore, we highlight that Skp2 may represent an attractive therapeutic target, thus warrants further development of agents to target Skp2, which could have significant therapeutic impact on prostate cancer.

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Section: The Role Of Skp2 In the Development And Progression Of Prmentioning

confidence: 99%

Skp2: A novel potential therapeutic target for prostate cancer

Wang

Gao

Fukushima

et al. 2012

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

115

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“…Those tumors with high SKP2 expression generally show low levels of p27 (Gstaiger et al, 2001;Hershko et al, 2001;Latres et al, 2001;Chiarle et al, 2002;Lim et al, 2002;Lu et al, 2002;Masuda et al, 2002;Penin et al, 2002;Signoretti et al, 2002;Yang et al, 2002). It would be important to determine whether the levels of p130 are affected in tumors overexpressing SKP2 and whether changes in the expression of p27 and p130 correlate in these cells.…”

Section: Implications For Tumorigenesismentioning

confidence: 99%

SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells

et al. 2003

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p130 is a member of the retinoblastoma family of pocket proteins, which includes pRB and p107. Unlike pRB and p107, p130 protein levels decrease dramatically following its hyperphosphorylation starting in the mid-G1 phase of the cell cycle. However, the mechanism leading to p130 downregulation is unknown. We have found that the proteasome inhibitor, lactacystin, inhibited p130 downregulation in T98G cells progressing through the G1/S transition and S phase and that p130 is multiubiquitylated in 293 cells. We have previously shown that ectopic expression of both cyclin D and E induces phosphorylation and downregulation of p130. Since the SKP1/Cul1/SKP2 E3 ubiquitin ligase complex mediates ubiquitylation of substrates previously phosphorylated by cyclin-dependent kinases, we investigated the potential role of this ubiquitin ligase in mediating p130 downregulation. We found that p130 interacts with SKP1, Cul-1 and SKP2 in human 293 cells. We also found that ectopic coexpression of SKP2 and p130 leads to dose-dependent downregulation of p130, reduces p130 protein half-life and induces p130 ubiquitylation in these cells. Moreover, adenoviral-mediated expression of SKP2 accelerates downregulation of endogenous hyperphosphorylated p130 in mitogen-stimulated T98G cells and primary WI38 fibroblasts. We conclude that p130 is a substrate of the SCF SKP2 ubiquitin ligase and this E3 ligase regulates p130 abundance during the cell cycle.

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“…For production of adenoviruses, the ADEASY system was used as previously described 26 . The NKX3.1 cDNA was cloned into the pADTRACK1 shuttle vector.…”

Section: Methodsmentioning

confidence: 99%

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

Yang

Chung²,

et al. 2014

F1000Res

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NKX3.1 is a homeobox transcription factor whose function as a prostate tumor suppressor remains insufficiently understood because neither the transcriptional program governed by NKX3.1, nor its interacting proteins have been fully revealed. Using affinity purification and mass spectrometry, we have established an extensive NKX3.1 interactome which contains the DNA repair proteins Ku70, Ku80, and PARP, thus providing a molecular underpinning to previous reports implicating NKX3.1 in DNA repair. Transcriptomic profiling of NKX3.1-negative prostate epithelial cells acutely expressing NKX3.1 revealed a rapid and complex response that is a near mirror image of the gene expression signature of human prostatic intraepithelial neoplasia (PIN). Pathway and network analyses suggested that NKX3.1 actuates a cellular reprogramming toward luminal cell differentiation characterized by suppression of pro-oncogenic c-MYC and interferon-STAT signaling and activation of tumor suppressor pathways. Consistently, ectopic expression of NKX3.1 conferred a growth arrest depending on TNFα and JNK signaling. We propose that the tumor suppressor function of NKX3.1 entails a transcriptional program that maintains the differentiation state of secretory luminal cells and that disruption of NKX3.1 contributes to prostate tumorigenesis by permitting luminal cell de-differentiation potentially augmented by defects in DNA repair.

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The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells

Cited by 71 publications

References 49 publications

Skp2: A novel potential therapeutic target for prostate cancer

Skp2: A novel potential therapeutic target for prostate cancer

SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells

Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation

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