Blake T J, Heath K G, Langdon W Y
Hanson Centre for Cancer Research, IMVS, Adelaide, Australia.
EMBO J. 1993 May;12(5):2017-26. doi: 10.1002/j.1460-2075.1993.tb05851.x.
The v-cbl oncogene is the transforming gene of the murine Cas NS-1 retrovirus which induces pre-B cell lymphomas and myeloid leukaemias. Sequencing of c-cbl has revealed that v-cbl was generated by a large truncation that removed 60% of the C-terminus of the corresponding protein. In this study we prepared antibodies to cbl and found that c-cbl encodes a 120 kDa protein which is localized in the cytoplasm with a cytosolic and cytoskeletal distribution. Immunofluorescence studies show a striking pattern of brightly staining vesicles in mitotic cells similar to that observed with cytokeratin antibodies. In contrast to p120c-cbl, which is exclusively cytoplasmic, the p100gag-v-cbl encoded by Cas NS-1 is localized in both the cytoplasm and the nucleus. This redistribution to the nucleus correlates with the ability of cbl to induce acute transformation. Furthermore the truncated protein encoded by v-cbl can bind DNA, unlike the full-length protein. These results suggest that the C-terminus of cbl is involved in the retention of p120c-cbl in the cytoplasm and the inhibition of DNA binding. The findings also suggest that a truncated protein encoded by c-cbl exists in the nucleus of normal cells.
v-cbl癌基因是鼠类Cas NS-1逆转录病毒的转化基因，可诱发前B细胞淋巴瘤和髓细胞白血病。对c-cbl的测序显示，v-cbl是通过大的截短产生的，该截短去除了相应蛋白质C末端的60%。在本研究中，我们制备了针对cbl的抗体，发现c-cbl编码一种120 kDa的蛋白质，其定位于细胞质中，呈胞质和细胞骨架分布。免疫荧光研究显示，有丝分裂细胞中存在一种与细胞角蛋白抗体观察到的类似的显著的明亮染色囊泡模式。与仅存在于细胞质中的p120c-cbl不同，由Cas NS-1编码的p100gag-v-cbl定位于细胞质和细胞核中。这种向细胞核的重新分布与cbl诱导急性转化的能力相关。此外，与全长蛋白质不同，v-cbl编码的截短蛋白质能够结合DNA。这些结果表明，cbl的C末端参与了p120c-cbl在细胞质中的保留以及对DNA结合的抑制。这些发现还表明，c-cbl编码的截短蛋白质存在于正常细胞的细胞核中。
