K-ras4b Proteins Are Expressed in the Nucleolus: Interaction with Nucleolin.
From: Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 2170, USA. birchena@mail.ncifcrf.gov
Biochemical and biophysical research communications
- Publish Date: Sep 2006
- ISSN: 0006-291X
- Volume: 348
- Issue: 2
- Pages: 540-9
- Medium: Print
- Language: English
- Citation (JAMA): Birchenall-Roberts Maria C, Fu Tao, Kim Soo-Gyung, et al. K-ras4b Proteins Are Expressed in the Nucleolus: Interaction with Nucleolin.. Biochem. Biophys. Res. Commun. Sep 2006;348:540-9
Abstract
Kirsten Ras4B (K-Ras4B) is a potent onco-protein that is expressed in the majority of human cell types and is frequently mutated in carcinomas. K-Ras4B, like other members of the Ras family of proteins, is considered to be a cytoplasmic protein that must be localized to the plasma membrane for activation. Here, using confocal microscopy and biochemical analysis, we show that K-Ras4B, but not H-Ras or the closely related K-Ras4A, is also present in the nucleoli of normal and transformed cells. Subcellular fractionation and immunostaining show that K-Ras4B is located not only in the cytoplasm, but also in the nucleolar compartment. Modification of a C-terminal hexa-lysine motif unique to K-Ras4B results in exclusively cytoplasmic forms of the protein. Nucleolin, a pleiotropic regulator of cellular processes, including transcriptional regulation, is also characterized by a nucleolar-like nuclear appearance. We show that K-Ras4B and nucleolin co-localize within the nucleus and that nucleolin physically associates with K-Ras4B. Inhibition of K-Ras4B/nucleolin association blocked nucleolar localization of K-Ras4B. Using siRNA to knockdown the expression of nucleolin eliminated the nucleolar localization of K-Ras4B and significantly repressed the activation of the well-characterized K-Ras4B transcriptional target Ap-1, but stimulated Elk1. These data provide evidence of a nucleolar localization of K-Ras4B and describe a functional association between K-Ras4B and nucleolin.
Mesh Headings (Keywords): Cell Nucleolus, Cells, Cultured, Humans, Nuclear Localization Signals, Phosphoproteins, Proto-Oncogene Proteins p21(ras), RNA-Binding Proteins, ras Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16889753
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