In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 11 ( 2014-03-18), p. 4179-4184
Abstract:
Neuroblastoma rat sarcoma (RAS) viral oncogene homolog (NRAS), a small GTPase, is one of the most thoroughly studied oncogenes that controls cell growth, differentiation, and survival by facilitating signal transduction. Here, we identify four novel naturally occurring NRAS isoforms (isoforms 2–5) in addition to the canonical isoform (isoform 1). Expression analyses performed on a panel of several different human malignancies and matching normal tissue revealed distinct isoform expression patterns. Two of the novel isoforms were found in the nucleus and cytoplasm, whereas the others were exclusively cytoplasmic. The isoforms varied in their binding affinities to known downstream targets and differentially regulated the RAS signaling pathway. Strikingly, forced expression of isoform 5, which encodes only a 20-aa peptide, led to increased cell proliferation and to transformation by activation of known NRAS targets. These discoveries open new avenues in the study of NRAS.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1401727111
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2014
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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