GBP-5 Splicing Variants: New Guanylate-Binding Proteins with Tumor-Associated Expression and Antigenicity

Abstract

We have identified a new gene, gbp-5, with high homology to the guanylate binding proteins (GBP) belonging to the GTPase superfamily including the ras gene. gbp-5 is transcribed at least into three splicing variants (gbp-5a, -5b, and -5ta) leading to two different proteins (GBP-5a/b, GBP-5ta). GBP-5ta is C-terminally truncated by 97aa and has therefore lost its isoprenylation site. Although RT-PCR results indicated expression of GBP-5 members in selected normal tissues, western blotting using two newly generated antibodies revealed that expression of both proteins is restricted to peripheral blood monocytes with GBP-5ta at lower levels. In contrast, cutaneous T-cell lymphoma (CTCL) tumor tissues (seven of seven) were positive solely for GBP-5ta, and four of four CTCL cell lines expressed both proteins. Eight of nine melanoma cell lines expressed GBP-5a/b and four of nine additionally low levels of GBP-5ta. SEREX retesting using CTCL sera indicated a higher immunogenicity for GBP-5ta (nine of 16) than for GBP-5a/b (two of 11). Treatment of CTCL cell lines with interferon-gamma did not alter protein expression of GBP-5ta or GBP-5a/b. The restricted expression pattern of both GBP-5ta and GBP-5a/b and the pivotal role of many known members of the GTP-binding proteins in proliferation and differentiation suggest possible cancer-related functions of gbp-5.

Endogenous retroviral LTRs as promoters for human genes: A critical assessment

“…The only exception is HSD17B1 which has an LTR promoter that appears to contribute placenta-specific expression in addition to normal expression in the ovary (Fournet-Dulguerov et al, 1987;Peltoketo et al, 1999;Sawetawan et al, 1994). We confirmed evidence that the LTR12C (HERV-9) promoter of GBP5 confers an expression pattern in lymphocytes, endothelial cells and a lymphoma cell line that is similar to that of its paralog, GBP1 (Fellenberg et al, 2004;LubesederMartellato et al, 2002;Olszewski et al, 2006;Tripal et al, 2007), data not shown). There is EST evidence that BAAT and MSLN have non-TE alternative promoters as well as their characterized LTR promoters (Kent et al, 2002).…”

The regulatory epicenter of miRNAs

“…SOX9 and the associated miRNA have been implicated in various carcinoma such as colorectal cancer and stand as critical components of regulation of cell cycle, differentiation and development (Jay et al 2005). Transcription factors like GBP have been associated with signalling and proliferation and have been identified as a promising target in cancer therapy (Fellenberg et al 2004;Guimarães et al 2009). Similarly, Lmo-2 expression has been noted to be very high in pancreatic cancer cells and exhibits strong correlation to aggression of prostate cancer and tumour angiogenic conditions (Yamada et al 2002;Ma et al 2007;Nakata et al 2009).…”

Role of Individual Domains and Identification of Internal Gap in Human Guanylate Binding Protein-1

“…6 hGBP-5 has been found at high levels in cutaneous T-cell lymphoma tumor cells. 8 Other members have been identified by bioinformatics search. 5 Among hGBPs, only hGBP-1 and hGBP-2 have been shown to exhibit GTPase activity, and a unique feature of the two proteins is their ability to hydrolyze GTP to a mixture of GDP and GMP.…”