Compartmentalization of hnRNP-K during cell cycle progression and its interaction with calponin in the cytoplasm.
Coronary artery blockage, due to cardiovascular disease, is routinely treated by either balloon-angioplasty or bypass surgery. The limited success of these clinical interventions is due at least in part to smooth muscle cell (SMC) proliferation. Here we show that heterogeneous nuclear ribonucleoprotein complex K (hnRNP-K) protein levels increase in SMC with response to serum stimulation in vitro, in the aortas from an animal model of atherosclerosis, and in occluded human vein segments. hnRNP-K is a multi-functional protein that has been studied primarily in cancer cells and has been suggested to play a role in cell cycle progression. We show that in untransformed, cultured SMC, hnRNP-K protein sub-cellular localization modulates through the cell cycle in both the cytoplasm and nucleus. Using cycloheximide, we observed that cytoplasmic accumulation of hnRNP-K protein at later time points in the cell cycle occurred with a concomitant decrease in nuclear hnRNP-K protein, suggesting a translocation of nuclear hnRNP-K protein to the cytoplasm. Also, because we did not observe an increase in hnRNP-K protein at early time points in the cell cycle in the presence of cycloheximide, we propose that the early increase in cytoplasmic hnRNP-K protein following serum stimulation is due to new hnRNP-K protein synthesis. When present in the cytoplasm, hnRNP-K is part of a multi-protein complex that consists of at least two other proteins, calponin and ERK1/2. Our findings from this study are intriguing because they suggest that cytoplasmic hnRNP-K in SMC is part of a signaling complex that may be involved in growth-stimulated post-transcriptional regulation.
Laury-Kleintop
Lisa D
LD
Lankenau Institute for Medical Research, 100 E. Lancaster Avenue, Wynnewood, Pennsylvania 19096, USA. KleintopL@mlhs.org
Tresini
Maria
M
Hammond
Olivia
O
D000818:Animals; D001011:Aorta / Q000378:metabolism; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport; D011817:Rabbits; D013347:Subcellular Fractions; D000096985:Calponins
D002135:Calcium-Binding Proteins; D002791:Cholesterol, Dietary; D003513:Cycloheximide; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000096985:Calponins