Subcellular localization of the Schlafen protein family

Neumann, Brent; Zhao, Liang; Murphy, Kathleen M.; Gonda, Thomas J.

doi:10.1016/j.bbrc.2008.03.032

Cited by 65 publications

(84 citation statements)

References 37 publications

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“…Finally, members of group III exhibit a C-terminal extension containing motif, homologous to the superfamily I of DNA/RNA helicases (5-7). Additionally, the C-terminal extensions also harbor a nuclear localization signal (RKRRR) further supporting the notion of nuclear function for the group of long Slfns (7).…”

Section: There Is Emerging Evidence That the Ifn-inducible Family Ofmentioning

confidence: 55%

Expression and Regulatory Effects of Murine Schlafen (Slfn) Genes in Malignant Melanoma and Renal Cell Carcinoma

Mavrommatis

Arslan

Sassano

et al. 2013

Journal of Biological Chemistry

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Background:The role of Slfn genes in antineoplastic responses is yet to be defined. Results: Murine Slfn genes are up-regulated in an IFN-dependent manner in melanoma, and RCC cells and members of this family differentially suppress proliferation and anchorage-independent malignant cell growth. Conclusion: Slfns play important roles in controlling malignant melanoma and RCC tumorigenesis. Significance: Modulation of Slfn expression may provide a novel approach for the treatment of malignancies.

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Section: There Is Emerging Evidence That the Ifn-inducible Family Ofmentioning

confidence: 55%

Expression and Regulatory Effects of Murine Schlafen (Slfn) Genes in Malignant Melanoma and Renal Cell Carcinoma

Mavrommatis

Arslan

Sassano

et al. 2013

Journal of Biological Chemistry

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“…In general, patients with recurrent or advanced disease have limited treatment options and a very poor overall prognosis (7). The Schlafen (SLFN) family of genes includes several members that share structural homology and play regulatory roles in the control of cell cycle progression and cell growth arrest (8)(9)(10)(11)(12). There are several human and mouse genes that are members of the SLFN family (9,11).…”

mentioning

confidence: 99%

“…The Schlafen (SLFN) family of genes includes several members that share structural homology and play regulatory roles in the control of cell cycle progression and cell growth arrest (8)(9)(10)(11)(12). There are several human and mouse genes that are members of the SLFN family (9,11). Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells

Sassano

Mavrommatis

Arslan

et al. 2015

Molecular and Cellular Biology

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We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of the matrix metalloproteinase 1 gene (MMP-1), MMP-13, and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Interferons (IFNs) are cytokines with important antineoplastic activities and therefore are frequently utilized in the treatment of cancer (1-4). A malignancy that exhibits sensitivity to interferon treatment is renal cell carcinoma (RCC) (5). RCC is the most common type of kidney tumor in humans and is associated with high morbidity and mortality (6, 7). In general, patients with recurrent or advanced disease have limited treatment options and a very poor overall prognosis (7). The Schlafen (SLFN) family of genes includes several members that share structural homology and play regulatory roles in the control of cell cycle progression and cell growth arrest (8-12). There are several human and mouse genes that are members of the SLFN family (9, 11). Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18). Notably, expression of various members of this family is upregulated following treatment with type I IFNs (17-19), cytokines known to promote induction of antineoplastic, antiviral, and immunoregulatory effects (1-4). Despite the induction of human and mouse SLFN genes by IFNs, the precise mechanisms by which SLFNs mediate antineoplastic responses in different types of malignant human cells remain to be determined.In the present study, we provide evidence that the expression of human SLFN5 is inducible by type I IFN receptor. SLFN5, like other long SLFNs, is characterized by a large C-terminal extension, a DNA/RNA helicase domain, and a nuclear localization sequence (NLS) (9, 20). Although SLFN5 is induced in melanoma cells following IFN treatment (18), the role of SLFN5 in tumor progression is largely unknown.In efforts to define the functional implications of SLFN5 expression in malignant RCC cells, we found that SLFN5 repressed the motility and invasiveness of malignant renal cell carcinoma cells, by negatively controlling the expression of matrix metalloproteinase (MMP) genes, such as MMP-1 and MMP-13. Importantly, analysis of SLFN5 mRNA expression in a large number of samples from a cohort of RCC patients demonstrated that SLFN5 expression correlates with better overall survival of RCC patients. Altogether, our studies for the first time establish a mechanism by which...

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“…Slfn-3 belongs to a murine multigene family, consisting of 10 genes, which contain several highly conserved SWADL domains defined by a five-amino acid (Ser-Trp-Ala-Asp-Leu) signature, which is thought to be schlafen protein specific (16,30). The schlafen protein family has been classified into three groups based on overall sequence homology and size of the encoded proteins: the shortest proteins are in group I (Slfn-1, -2, and schlafen-like-1), while schlafen proteins of intermediate size (Slfn-3, -4, -6, and -7) are in group II.…”

mentioning

confidence: 99%

“…All schlafen proteins have a common "schlafen box", which lies adjacent to a GTP/ATP binding AAA domain that functions similarly to the classical AAA domains in GTP/ATP binding protein. Classical AAA domaincontaining proteins perform a variety of functions, including protein degradation and folding, vesicle transport/fusion, and transcription (16,30). Among schlafen family of proteins, Slfn-3 has been shown to regulate cell growth and differentiation in vitro, presumably through the inhibition of cyclin D1 (4,31,32).…”

mentioning

confidence: 99%

Schlafen-3 decreases cancer stem cell marker expression and autocrine/juxtacrine signaling in FOLFOX-resistant colon cancer cells

Patel

Sanders

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Subcellular localization of the Schlafen protein family

Cited by 65 publications

References 37 publications

Expression and Regulatory Effects of Murine Schlafen (Slfn) Genes in Malignant Melanoma and Renal Cell Carcinoma

Expression and Regulatory Effects of Murine Schlafen (Slfn) Genes in Malignant Melanoma and Renal Cell Carcinoma

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells

Schlafen-3 decreases cancer stem cell marker expression and autocrine/juxtacrine signaling in FOLFOX-resistant colon cancer cells

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