Exploring the association between genetic variation in the <scp>SUMO</scp> isopeptidase gene <scp><i>USPL1</i></scp> and breast cancer through integration of data from the population‐based <scp>GENICA</scp> study and external genetic databases

Bermejo, Justo Lorenzo; Kabisch, Maria; Dünnebier, Thomas; Schnaidt, Sven; Melchior, Frauke; Fischer, Hans‐Peter; Harth, Volker; Rabstein, Sylvia; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Baisch, Christian; Ko, Yon‐Dschun; Hamann, Ute

doi:10.1002/ijc.28040

Cited by 13 publications

(10 citation statements)

References 49 publications

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“…Recent studies have demonstrated that human USPL1 is a cysteine protease belonging to ubiquitin-specific protease (USP) family that plays a key role in snRNA transcription, telomere integrity and cell proliferation3536. A role in such fundamental cell viability requirements is consistent with an early developmental failure and suggests either that maternal protein allows dsUspl1 embryos to progress until morula stage or that other genes are redundant until blastocyst formation.…”

Section: Resultsmentioning

confidence: 99%

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

Cui

Dai

Marcho

et al. 2016

Sci Rep

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With readily available transcriptome-wide data, understanding the role of each expressed gene is an essential next step. Although RNAi technologies allow for genome-wide screens in cell culture, these approaches cannot replace strategies for discovery in the embryo. Here we present, for the first time, a knockdown screen in mouse preimplantation embryos. Early mammalian development encompasses dynamic cellular, molecular and epigenetic events that are largely conserved from mouse to man. We assayed 712 genes for requirements during preimplantation. We identified 59 genes required for successful development or outgrowth and implantation. We have characterized each phenotype and revealed cellular, molecular, and lineage specific defects following knockdown of transcript. Induced network analyses demonstrate this as a valid approach to identify networks of genes that play important roles during preimplantation. Our approach provides a robust and efficient strategy towards identification of novel phenotypes during mouse preimplantation and facilitates functional annotation of the mammalian transcriptome.

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Section: Resultsmentioning

confidence: 99%

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

Cui

Dai

Marcho

et al. 2016

Sci Rep

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“…Indeed, C allele homozygosis is associated with a lower risk of breast tumors with respect to the TT homozygotes, probably because the C allele was associated with increased USPL1 expression [96].…”

Section: Sumo Proteasesmentioning

confidence: 99%

“…Oral squamous cell carcinoma Diagnosis [92] Breast Prognosis [93] SENP6 Breast Diagnosis [94] SENP7 Breast Diagnosis [95] USPL1 Breast Risk assessment [96] SUMO1, SUMO2/3 Astrocytic brain Diagnosis, progression [60] SUMO1 Hepatocellular carcinoma Diagnosis [97] Lip Diagnosis [98] Oral squamous cell carcinoma Diagnosis, prognosis [99] AML: Acute myeloid leukemia; MDS: Myelodysplastic syndrome.…”

Section: Senp5mentioning

confidence: 99%

SUMO pathway components as possible cancer biomarkers

Mattoscio

Chiocca

2015

Future Oncol.

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SUMOylation is a key post-translational modification that regulates crucial cellular functions and pathological processes. Recently, Small Ubiquitin-related MOdifier (SUMO) modification has emerged as a fundamental route that may drive different steps of human tumorigenesis. Indeed, alteration in expression or activity of one of the different SUMO pathway components may completely subvert cellular properties through fine-tuning modulation of protein(s) involved in carcinogenic pathways, leading to altered cell proliferation, apoptosis resistance and metastatic potential. Here we describe some of the most interesting findings pointing to a clear link between SUMO pathway and human malignancies. Importantly, a putative role for SUMO enzymes to predict cancer behavior can be speculated, and thus the possible application of alterations in SUMO pathway components as tumor biomarkers is discussed.

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“…Cancer type Deregulation References oral Overexpression of SENP3 Overexpression of SENP5 [139][140][141] breast Low expression of SENP5 contributes to better survival [142] Downregulation of SENP6 [143] USPL1 breast Expression contributes to risk of Grade 3 breast tumors [144] …”

Section: Proteinsmentioning

confidence: 99%

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

Eifler

Vertegaal

2015

Trends in Biochemical Sciences

234

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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Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population‐based GENICA study and external genetic databases

Cited by 13 publications

References 49 publications

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

SUMO pathway components as possible cancer biomarkers

SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer

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