K-Ras4B proteins are expressed in the nucleolus: Interaction with nucleolin

Journal Article · Fri Sep 22 00:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.07.094· OSTI ID:20854473

Birchenall-Roberts, Maria C ^[1]; Fu, Tao ^[1]; Kim, Soo-Gyung ^[1]; Huang, Ying K ^[2]; Dambach, Michael ^[2]; Resau, James H ^[3]; Ruscetti, Francis W ^[2]

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1. Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 2170 (United States)
2. Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702 (United States)
3. Van Andel Institute, Grand Rapids, MI 49506 (United States)

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.

• OSTI ID: 20854473
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 348, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.07.094; PII: S0006-291X(06)01634-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
CARCINOMAS
CYTOPLASM
GENE REGULATION
INTERACTIONS
LYSINE
MICROSCOPY
NUCLEOLI
PROTEINS