Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions.
Rhombotin-2 (RBTN-2) is a LIM domain protein that, with the exception of thymocytes, is widely expressed during fetal development. Although RBTN-2 is crucial for normal erythropoiesis, the ectopic expression of RBTN-2 in T lymphocytes results in T-cell proliferation and leukemogenesis. Thus, while a proliferative function for RBTN-2 has been established in T-cells, neither its role in erythropoiesis nor its function(s) in other tissues are known. We have examined the expression and location of RBTN-2 in normal and malignant cells. Similar to fetal development, RBTN-2 RNA was detected in all normal adult tissues tested with the exception of colon and thymocytes. RBTN-2 RNA was not detected in all primary tumors and tumor cell lines, indicating RBTN-2 expression is not ubiquitous in proliferating cells. Using polyclonal antisera, RBTN-2 was detected predominantly in the nucleus of human hematopoietic cells. Significantly, human leukemic T cells with disruption of the RBTN-2 locus and thymocytes from transgenic mice with enforced expression of RBTN-2 showed similar nuclear location of RBTN-2 protein, consistent with the notion that RBTN-2 acts as a transcriptional regulator in T-cell proliferation. Surprisingly, in normal tissues, RBTN-2 showed a strikingly similar distribution to that of metallothionein-1, having both nuclear and cytoplasmic localization that suggested that RBTN-2 may be involved in the acute phase response. Indeed, similar to metallothionein-1, RBTN-2 mRNA was induced in thymocytes of mice exposed to zinc and in human thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Since the LIM domain permits binding of multiple protein partners, the specific function of RBTN-2 may depend upon subcellular sequestration through interaction with different cofactors. Thus, in addition to its roles in erythropoiesis and T-cell leukemia, RBTN-2 may also be involved in the acute phase response.
Neale
G A
GA
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Mao
S
S
Parham
D M
DM
Murti
K G
KG
Goorha
R M
RM
D000209:Acute-Phase Proteins / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D001923:Brain Chemistry; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics; D002675:Child, Preschool; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D004920:Erythropoiesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000737:chemistry; D060588:LIM Domain Proteins; D015458:Leukemia, T-Cell / Q000235:genetics; D008099:Liver / Q000737:chemistry; D008667:Metalloproteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000737:chemistry; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D000209:Acute-Phase Proteins; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; C513188:Lmo2 protein, mouse; C000715470:MAS1 protein, human; D008667:Metalloproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D008668:Metallothionein; D003513:Cycloheximide; D015032:Zinc; D013755:Tetradecanoylphorbol Acetate