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-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.
Fellenberg
Friederike
F
German Cancer Research Center, Skin Cancer Unit, Heidelberg, Germany.
Hartmann
Tanja B
TB
Dummer
Reinhard
R
Usener
Dirk
D
Schadendorf
Dirk
D
Eichmüller
Stefan
S
D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology; D001706:Biopsy; D019204:GTP-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*
D000970:Antineoplastic Agents; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C472531:Gbp5 protein, mouse