GBP-5 splicing variants: new guanylate-binding proteins with tumor-associated expression and antigenicity

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-5...

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Main Authors: Fellenberg, Friederike (Author) , Schadendorf, Dirk (Author) , Eichmüller, Stefan B. (Author)
Format: Article (Journal)
Language:English
Published: 2004
In: The journal of investigative dermatology
Year: 2004, Volume: 122, Issue: 6, Pages: 1510-1517
ISSN:1523-1747
DOI:10.1111/j.0022-202X.2004.22613.x
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/j.0022-202X.2004.22613.x
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X15308587
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Author Notes:Friederike Fellenberg, Tanja B. Hartmann, Reinhard Dummer, Dirk Usener, Dirk Schadendorf, and Stefan Eichmüller
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Summary: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-γ 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.
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ISSN:1523-1747
DOI:10.1111/j.0022-202X.2004.22613.x