SENP2 Regulates Hepatocellular Carcinoma Cell Growth by Modulating the Stability of β-catenin

Shen, Huojian; Zhu, Hongyi; Yang, Chia-Han; Ji, Fu

doi:10.7314/apjcp.2012.13.8.3583

Cited by 41 publications

(42 citation statements)

References 22 publications

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“…Specifically, SENP2 was found to be downregulated in HCC tissues, while its overexpression is believed to prevent growth and colony formation of HCC cells. In contrast, SENP2 knockdown leads cancer cell growth (14).…”

Section: Sumoylation and Protein Stabilitymentioning

confidence: 95%

“…Intriguingly, in liver cancer patients the survival rate is strongly correlated with SUMO-2 expression. In addition, UBC9, the sole E2 enzyme in SUMOylation machinery, has been described overexpressed in HCC during SUMO modification (12), while SENP2, that controls the deSUMOylation process, inhibits the proliferation of HCC cells (13,14). Moreover, SUMOylation appears to play a key role in HCC multidrug resistance (15).…”

Section: Sumoylation Machinerymentioning

confidence: 99%

“…β-catenin SUMO proteases (SENP) are known to be responsible of SUMO remotion from SUMOylated proteins, and their expression is described to be deregulated in many cancers (14,41). Specifically, SENP2 was found to be downregulated in HCC tissues, while its overexpression is believed to prevent growth and colony formation of HCC cells.…”

Section: Sumoylation and Protein Stabilitymentioning

confidence: 99%

“…WWOX has been described as an important downstream modulator of SENP2 tumor suppressor function, and a key player on SENP2-β-catenin asset that controls liver cancer growth. Basically, SENP2 negatively regulates Wnt/β-catenin pathway transcriptional activity by inducing WWOX transcription, thereby resulting in β-catenin protein destabilization (13,14). In contrast, WWOX silencing reverses the effect of SENP2 on β-catenin stability and cancer cells growth (13).…”

Section: Sumoylation and Protein Stabilitymentioning

confidence: 99%

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SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma

Tomasi

Ramani

2018

Transl. Gastroenterol. Hepatol.

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Section: Sumoylation and Protein Stabilitymentioning

confidence: 95%

Section: Sumoylation Machinerymentioning

confidence: 99%

Section: Sumoylation and Protein Stabilitymentioning

confidence: 99%

Section: Sumoylation and Protein Stabilitymentioning

confidence: 99%

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SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma

Tomasi

Ramani

2018

Transl. Gastroenterol. Hepatol.

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“…prostate Overexpression of SENP1 [131,132] Overexpression of SENP3 [101] colon Overexpression of SENP1 [133] Overexpression of SENP3 [134] liver Downregulation of SENP2 [135] Overexpression of SENP6 [136] bladder Downregulation of SENP2 [137] gastric Overexpression of SENP3 [138] Trends Biochem Sci. Author manuscript; available in PMC 2016 June 01.…”

Section: Figure 2 Sumoylation Of Important Cell Cycle Regulatorsmentioning

confidence: 99%

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

Eifler

Vertegaal

2015

Trends in Biochemical Sciences

246

211

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SUMOylation plays critical roles during cell cycle progression. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate cell cycle progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. Different types of cancers were recently shown to be dependent on a functioning SUMOylation system, a finding that could potentially be exploited in anti-cancer therapies. KeywordsSUMO; mitosis; SUMOylation; cancer; cell cycle SUMO: a ubiquitin-like modifier that regulates nuclear processesThe complexity of eukaryotic proteomes is widely expanded by protein processing and a vast array of posttranslational modifications. The quick and reversible attachment of small modifiers is essential for all cellular processes and ensures dynamic and rapid responses to extracellular and intracellular stimuli. Apart from chemical modifications such as phosphorylation [1], glycosylation [2] and acetylation [3], small polypeptides can be attached to proteins, resulting in a change in the activity, localization, half-life or interactome of the target protein. Since the initial discovery of ubiquitin, the founding member of these small protein posttranslational modifications in 1975 [4], a large family of structurally related ubiquitin-like modifiers has been uncovered including SUMO, Nedd8, ISG15, FAT10, FUB1, UFM1, URM1, Atg12 and Atg8 [5][6][7][8]. The attachment of these small ubiquitin-like modifiers is catalysed by an enzymatic cascade consisting of an activating enzyme (E1), a conjugating enzyme (E2) and a ligase (E3), and can be reversed by specific and cell cycle control. It is therefore not surprising that SUMO signal transduction has been implicated in the development of several different cancer types, which could potentially be exploited in anti-cancer therapies. In this review we will focus on the role of SUMO in cell cycle regulation, specifically highlighting its physiological relevance and its deregulation in cancer. Recent progress includes the identification of many novel SUMO substrates with important roles in cell cycle progression using proteomic approaches, and the demonstration that different mouse cancer models are dependent on a functioning SUMOylation system. Switching of SUMOylation in these cancer models caused a proliferation block of the cancer cells, showing that SUMO conjugating enzymes are potential drug targets. Europe PMC Funders Group Twenty years of SUMO research in cell cycle controlSUMO was linked to cell cycle progression even before the identification of the small protein modifier itself. Twenty years ago, the yeast SUMO conjugating enzyme Ubc9 was first proposed to be a ubiquitin conjugating enzyme. Ubc9 was s...

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