Interaction between the cationic surfactant cetyltrimethylammonium bromide (CTAB) and the anionic polyelectrolyte poly(acrylic acid) (PAA), having molecular weight by viscosity of 750 kDa, is investigated by rheological measurements. Upon addition of 1 or 0.5 wt % CTAB to the semidilute PAA solutions with concentration ranging from 0.04 to 0.1 wt %, the insoluble complex salts (the surfactant ion + the polyion) precipitate. In contrast, with addition of 2 or 3 wt % CTAB to the aforementioned PAA solutions, evidence of transition from shear-thinning to nearly Newtonian behavior is observed. The origin of this observation appears to lie in the fact of formation of more compact PAA/CTAB aggregates, because the radii of gyration, R g , of PAA coils have been reduced by about 60% with addition of 2 wt % CTAB by static light-scattering measurements. Furthermore, pH measurements also reveal the possible formation of "ion pairs" between PAA and CTAB as the pH values of the PAA solutions decrease with addition of CTAB. That is, the pH values of the solutions containing PAA and CTAB together are less than those of neat PAA or CTAB solutions. This implies that addition of CTAB leads to more acids dissociated from the acrylic acid monomers on the poly(acrylic acid) macromolecules.

IntroductionNucleophosmin (NPM) is a multifunctional protein that resides predominantly in the nucleoli. It performs a multitude of nuclear functions, such as processing and transporting of ribosomal RNA and proteins, 1 molecular chaperoning, 2 and regulating the stability of tumor suppressors, such as p53, 3 ARF, 4 and c-Myc. 5 However, its cytoplasmic role is largely unknown. In up to one-third of patients with acute myeloid leukemia (AML), a heterogeneous frame-shift mutation in the NPM1 gene results in skewed cytoplasmic accumulation of the NPM mutant protein (NPMc), and this is thought to function in cancer pathogenesis. 6 As NPM1 is the most frequently mutated gene in AML with a normal karyotype, uncovering NPM's diverse cellular functions may hold the key to unraveling specific leukemogenic mechanisms involving the mutant protein.Current AML research centers on the effect of nuclear NPM deprivation on genetic instability, derailment of cell cycle, and cancer progression. NPMc mutants were demonstrated to retain functional interactions with both their nuclear partners and wild-type NPM. Massive dislocation of the mutant protein to the cytoplasm was observed to deplete tumor suppressors and negative controllers of cell proliferation, such as p53, 7 ARF, 8 c-Myc-regulating Fbw7, 5 Miz1, 9 HEXIM1, 10 and NF-B, 11 from the nucleus. The ensuing impairment in cell proliferation control was thus hypothesized to drive carcinogenesis. However, the overexpression of NPMc alone failed to demonstrate any transformation activity or enhancement of cell proliferation 5,7 ; hence, these observations seemed incongruent with the aforementioned hypothesis. Furthermore, loss of p53 from the nucleus, which often results in genetic instability, is also not consistent with the fact that NPMc is exclusively associated with normal karyotypes. 12 More importantly, NPMc mutations are so far identified only in AML, 13 whereas ARF, c-Myc, and p53 defects are found in a multitude of cancers of diverse tissue origins. [14][15][16] Such discrepancies argue for the existence of a hematopoietic-specific mechanism involving the mutant NPM.Here, we identify NPMc as an inhibitor of active caspase-6 and -8, which are pivotal components of cell death signaling. Through the impediment of the caspase signaling cascade, the dislocated NPMc mutant not only raises the threshold for cell death initiation, but more interestingly, hinders the caspase-mediated myeloid differentiation process. Our data thus demonstrate a potential myeloid-specific oncogenic role for the NPMc mutant. Methods ReagentsAntibodies against NPM, caspase-3, -6, and -9 were purchased from Cell Signaling Technology, antibodies against cleaved caspase-3, caspase-8, poly(ADP-ribose) polymerase, and actin from Santa Cruz Biotechnology, antibody against caspase-7 from Neomarker, anti-Fas antibody from Upstate Biotechnology, and antibody against Oct-1 from Chemicon. Recombinant active caspase-3, -6, -7, -8, and -9, recombinant procaspase-3 protein, caspase-6 and -8 inhibitors, and reco...

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