The Schlafen family: complex roles in different cell types and virus replication

Abstract

The Schlafen (slfn) gene family members express broadly, but the research has mainly focused on human slfn (h-slfn) and mouse slfn (m-slfn). The slfn members can be divided into three groups, and each group has its own characteristics and functions. Although the effects of slfns are still poorly understood, it has been confirmed that slfns are involved in the defense of immune system and regulate immune cells' proliferation and differentiation. In some malignant tumors, the slfn proteins can inhibit the growth and invasion of cancer cells, promote cancer cells sensibility to chemotherapeutics, and can be a promising new therapeutic target. In addition, the slfn proteins also disturb replication and virulence of viruses. In this review, we summarize the characteristics of the Schlafen family's structures and functions with the aim to achieve a more comprehensive understanding of slfns.

Loss of Schlafen3 influences the expression levels of Schlafen family members in ileum, thymus, and spleen tissue

“…KLF6 interacts with KLF4 in order to co-activate keratin-4 which associates with the proliferation to differentiation switch in human esophageal squamous cancer cells (Ghaleb & Yang, 2008;Okano et al, 2000). Such observations would be consistent with a model in which there is a regulatory feedback loop between the KLF family and Slfn family members as they have all been recognized as regulators of gastrointestinal and immune cell differentiation (Bieker, 2001;Flandez et al, 2008;Ghaleb & Yang, 2008;Liu et al, 2018;Mavrommatis, Fish & Platanias, 2013;Okano et al, 2000). However, this awaits further exploration beyond the scope of the current manuscript.…”

“…Slfn3 is upregulated during CD4 + CD25 − T effector cell activation but downregulated upon activation and proliferation of CD4 + CD25 + T regulatory cells (Condamine et al, 2010). The role of Slfn4 has been demonstrated to restrain the maturation of T cells and the differentiation of macrophages (Liu et al, 2018;Van Zuylen et al, 2011). Additionally, Slfn3 is important in the regulation of intestinal differentiation, development and maturation Patel et al, 2009;Walsh et al, 2012;Yuan et al, 2010).…”

“…In comparison to the Group I and II Slfns that are localized to the cytoplasm, the Group III Slfns contain a nuclear localization signal in the C-terminus and have been shown to be co-localized with the phosphorylated RNA polymerase II and SC-35 within the nucleus (Neumann et al, 2008). Slfn5 and Slfn8 have also been demonstrated to be involved in the modulation of T cells by inhibiting their proliferation and regulating the T cell activation (Geserick et al, 2004;Liu et al, 2018).…”

Germline mutations and new copy number variants among 40 pediatric cancer patients suspected for genetic predisposition

“…Compared to normal adrenal gland tissues, all the three genes showed a reduced expression in NBL, mainly SLFN12 (Figure ). No genetic diseases have been associated with germline mutations in neither SLFN11 , SLFN12 or SLNF13 , but they are believed to regulate cell growth, to promote cell differentiation, to inhibit migration and invasion, to play a role in DNA repair …”

Slfn2 Regulates Type I Interferon Responses by Modulating the NF-κB Pathway

“…Understanding the roles of Slfn2 in different physiological/pathological contexts is important, since Slfn2 has been found to regulate distinct signaling pathways and to affect molecular mechanisms in a cell-type-specific/tissue-dependent manner (22). For example, in naive T cells, Slfn2 was shown to regulate quiescence by preventing endoplasmic reticulum stress that in turn regulates cholesterol levels (23).…”