CAPERα Is a Novel Rel-TAD-Interacting Factor That Inhibits Lymphocyte Transformation by the Potent Rel/NF-κB Oncoprotein v-Rel

Abstract

The Rel/NF-B family of transcription factors is key for immune and inflammatory responses and also controls cell proliferation and apoptosis. The v-Rel oncoprotein of reticuloendotheliosis virus strain T (Rev-T) is the most potent oncogenic member of this family. Both v-Rel and its cellular homologue c-Rel transform primary splenic lymphocytes in vitro and cause fatal leukemia/lymphomas in chickens and transgenic mice (5,9,17,22,23,33,38,39). This agrees with the implication of Rel/NF-B in the pathogenesis and chemoresistance of many hematopoietic and solid tumors, including primary mediastinal B-cell lymphomas (PMBCL) and classical Hodgkin's lymphoma, in which constitutively high levels of nuclear c-Rel protein are necessary for tumor cell survival and proliferation (3,4,14,18,20,27,49). Additionally, some PMBCL and follicular lymphomas harbor c-rel gene mutations that decrease c-Rel's transactivation potency and enhance its transforming activity in primary chicken lymphocytes (45). This is consistent with the increased transforming phenotype conferred by certain mutations in v-Rel and c-Rel and indicates that modulation of Rel's transcriptional activity can significantly affect its oncogenicity (12,43,44).The Rel proteins bind to B DNA sites as homo-or heterodimers with other NF-B family members via their N-terminal Rel homology domain (RHD), which also mediates nuclear localization and association with inhibitory IB subunits.

CAPER, a novel regulator of human breast cancer progression

“…22 In a separate study, CAPER has also been shown to interact with the C-terminal transactivation domain (TAD) of the NF-κB oncoprotein v-Rel and to suppress its transforming activity in vitro. 23 However, the region of CAPER involved in the co-activation of v-Rel was shown to be different than the one involved in the co-activation of ERα/β and c-Jun. 23 In fact, v-Rel was reported to interact with the N-terminal domain of CAPER, while ERα/β and c-Jun interact with its C-terminal domain.…”

“…23 However, the region of CAPER involved in the co-activation of v-Rel was shown to be different than the one involved in the co-activation of ERα/β and c-Jun. 23 In fact, v-Rel was reported to interact with the N-terminal domain of CAPER, while ERα/β and c-Jun interact with its C-terminal domain. 23 Interestingly, CAPER expression was also recently shown to be upregulated in human colorectal adenomas and carcinomas.…”

“…23 In fact, v-Rel was reported to interact with the N-terminal domain of CAPER, while ERα/β and c-Jun interact with its C-terminal domain. 23 Interestingly, CAPER expression was also recently shown to be upregulated in human colorectal adenomas and carcinomas. 25 The expression of CAPER was reported to affect the survival of colorectal cancer cells.…”

“…22 Importantly, CAPER appears rather selective for c-Jun, ERα/β, and PR and does not interact with other transcription factors such as p53, the AP-1 component c-fos, the NFκB component p50, serum response factor, retinoic acid receptor (RAR)-α, thyroid hormone receptor (TR)-α/β, PPAR-α, liver X receptor-α/β, farnesoid X receptor, and glucocorticoid receptor, among others. 19,22,23 Interestingly, CAPER was recently shown to be involved in human breast cancer progression. 20 Indeed, using a tissue microarray and automated quantivative bioimaging analysis (AQUA), we reported that CAPER protein levels were upregulated during the transition from pre-malignancy to IDC.…”

Unmasking the U2AF homology motif family: a bona fide protein–protein interaction motif in disguise

“…2F; Loerch et al 2014). These three proteins function in alternative splicing (Page-McCaw et al 1999;Lallena et al 2002;Dowhan et al 2005;Hastings et al 2007;Huang et al 2012); PUF60 and CAPERα also are coactivators of transcription (Liu et al 2000(Liu et al , 2001Jung et al 2002;Dowhan et al 2005;Dutta et al 2008). Other UHM-containing proteins participate in related pathways.…”