Knockdown of ubiquitin associated protein 2-like inhibits the growth and migration of prostate cancer cells

Liu, Dong; Huang, Yiran

doi:10.3892/or.2014.3360

Cited by 31 publications

(42 citation statements)

References 20 publications

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“…8c,d ). The observation that 9 candidate metastasis genes ( Pten , Gsk3b , Snap23 , Map4k3 , Arhgap35 ( Grlf1 ), Arhgef18 , Axin1 , Raf1 and Ubap2l ) have been implicated in metastasis of other cancers supports our conclusion that we have identified genes truly central to osteosarcoma metastasis 50–58 .…”

Section: Resultssupporting

confidence: 83%

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

et al. 2015

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Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.

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Section: Resultssupporting

confidence: 83%

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

et al. 2015

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“…We found that nearly all UBAP2L is modified by O-GlcNAc. Recent work indicated a potential role for UBAP2L in the epigenetic regulation of cell proliferation (81,82), and another study reported that UBAP2L is phosphorylated upon T cell activation (83), warranting future investigation of UBAP2L and its regulation by posttranslational modifications in T cells.…”

Section: Discussionmentioning

confidence: 99%

Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells

Lund

Elias

Davis

2016

The Journal of Immunology

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T cell activation in response to Ag is largely regulated by protein posttranslational modifications. Although phosphorylation has been extensively characterized in T cells, much less is known about the glycosylation of serine/threonine residues by O-linked N-acetylglucosamine (O-GlcNAc). Given that O-GlcNAc appears to regulate cell signaling pathways and protein activity similarly to phosphorylation, we performed a comprehensive analysis of O-GlcNAc during T cell activation to address the functional importance of this modification and to identify the modified proteins. Activation of T cells through the TCR resulted in a global elevation of O-GlcNAc levels and in the absence of O-GlcNAc, IL-2 production and proliferation were compromised. T cell activation also led to changes in the relative expression of O-GlcNAc transferase (OGT) isoforms and accumulation of OGT at the immunological synapse of murine T cells. Using a glycoproteomics approach, we identified >200 O-GlcNAc proteins in human T cells. Many of the identified proteins had a functional relationship to RNA metabolism, and consistent with a connection between O-GlcNAc and RNA, inhibition of OGT impaired nascent RNA synthesis upon T cell activation. Overall, our studies provide a global analysis of O-GlcNAc dynamics during T cell activation and the first characterization, to our knowledge, of the O-GlcNAc glycoproteome in human T cells.

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“…Ubiquitin‐associated protein 2‐like (UBAP2L) is a widely conserved protein with a ubiquitin‐associated (UBA) domain and multiple RGG/RG repeats in the N terminus. A recent study showed that UBAP2L is overexpressed in prostate cancer and that the depletion of UBAP2L suppresses migration and proliferation of cancer cells (26). UBAP2L was also reported to associate with the polycomb complex protein B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), for the maintenance of hematopoietic stem cell activity (27).…”

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confidence: 99%

Arginine methylation of ubiquitin‐associated protein 2‐like is required for the accurate distribution of chromosomes

et al. 2015

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Proper bioriented attachment of microtubules and kinetochores is essential for the precise distribution of duplicated chromosomes to each daughter cell. An aberrant kinetochore-microtubule attachment results in chromosome instability, which leads to cellular transformation or apoptosis. In this article, we show that ubiquitin-associated protein 2-like (UBAP2L) is necessary for correct kinetochore-microtubule attachment. Depletion of UBAP2L inhibited chromosome alignment in metaphase and delayed progression to anaphase by activating spindle assembly checkpoint signaling. In addition, UBAP2L knockdown increased side-on attachment of kinetochores along the microtubules and suppressed stable kinetochore fiber formation. A proteomics analysis identified protein arginine methyltransferase (PRMT)1 as a direct interaction partner of UBAP2L. UBAP2L has an arginine- and glycine-rich motif called the RGG/RG or GAR motif in the N terminus. Biochemical analysis confirmed that arginine residues in the RGG/RG motif of UBAP2L were directly methylated by PRMT1. Finally, we demonstrated that the RGG/RG motif of UBAP2L is essential for the proper alignment of chromosomes in metaphase for the accurate distribution of chromosomes. Our results show a possible role for arginine methylation in UBAP2L for the progression of mitosis.

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Knockdown of ubiquitin associated protein 2-like inhibits the growth and migration of prostate cancer cells

Cited by 31 publications

References 20 publications

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells

Arginine methylation of ubiquitin‐associated protein 2‐like is required for the accurate distribution of chromosomes

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