Nuclear localization and transactivating capacities of the papillary renal cell carcinoma-associated TFE3 and PRCC (fusion) proteins

• Published in: Oncogene Vol. 19; no. 1; pp. 69 - 74
• Main Authors: WETERMAN, M. A. J, VAN GRONINGEN, J. J. M, JANSEN, A, VAN KESSEL, A. G
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 06.01.2000; Nature Publishing Group
• Subjects: Amino acids; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biological and medical sciences; Carcinoma, Renal cell; Carcinoma, Renal Cell - genetics; Cell Cycle Proteins; Cell Nucleus - chemistry; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; chromosome 1; COS Cells; DNA binding proteins; DNA-Binding Proteins - analysis; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Genes; Genetic aspects; Immunoglobulins; Kidney cancer; Kidney Medulla; Kidney Neoplasms - genetics; Kinases; Localization; Molecular and cellular biology; Neoplasm Proteins; Phosphorylation; Physiological aspects; PRCC gene; Proteins; Proteins - analysis; Proteins - physiology; Recombinant Fusion Proteins - analysis; Recombinant Fusion Proteins - physiology; renal cell carcinoma; Risk factors; TFE3 gene; Trans-Activators - analysis; Trans-Activators - physiology; Transcription factors; Transcription Factors - analysis; Transcription Factors - physiology; Translocation (Genetics); Tumors; X chromosome; X chromosomes; Netherlands; Chromosomal aberration; Kidney disease; Papillary carcinoma; Cell nucleus; Monkey; Malignant tumor; Gene expression; Carcinogenesis; Kidney; Vertebrata; Regulation(control); Cell line; Mammalia; Gene; Primates; Abnormal chromosome; Transcription factor; Localization; Fusion protein; Chromosome translocation
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203255

The papillary renal cell carcinoma-associated t(X;1)(p11;q21) leads to fusion of the transcription factor TFE3 gene on the X-chromosome to a novel gene, PRCC, on chromosome 1. As a result, two putative fusion proteins are formed: PRCCTFE3, which contains all known domains for DNA binding, dimerization, and transactivation of the TFE3 protein, and the reciprocal product TFE3PRCC. Upon transfection into COS cells, both wild type and fusion proteins were found to be located in the nucleus. When comparing the transactivating capacities of these (fusion) proteins, significant differences were noted. PRCCTFE3 acted as a threefold better transactivator than wild type TFE3 both in a TFE3-specific and in a general (Zebra) reporter assay. In addition, PRCC and the two fusion proteins were found to be potent transactivators in the Zebra reporter assay. We propose that, as a result of the (X;1) translocation, fusion of the N-terminal PRCC sequences to TFE3 alters the transactivation capacity of the transcription factor thus leading to aberrant gene regulation and, ultimately, tumor formation.