Housing Justice in Unequal Cities

Housing Justice in Unequal Cities is a global research network funded by the National Science Foundation (BCS 1758774) and housed at the Institute on Inequality and Democracy at UCLA Luskin. This open-access volume, co-edited by Ananya Roy and Hilary Malson, brings together movement-based and university-based scholars to build a shared field of inquiry focused on housing justice. Based on a convening that took place in Los Angeles in January 2019, at the LA Community Action Network and at the University of California, Los Angeles, the essays and interventions situate housing justice in the long struggle for freedom on stolen land. Embedded in the stark inequalities of Los Angeles, our work is necessarily global, connecting the city’s Skid Row to the indebted and evicted in Spain and Greece, to black women’s resistance in Brazil, to the rights asserted by squatters in India and South Africa. Learning from radical social movements, we argue that housing justice also requires a commitment to research justice. With this in mind, our effort to build a field of inquiry is also necessarily an endeavor to build epistemologies and methodologies that are accountable to communities that are on the frontlines of banishment and displacement

Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

BACKGROUND: We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC) model established in our laboratory. METHODS: The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. RESULTS: In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. CONCLUSION: Our studies in both RCC and prostate tumor models demonstrate that the combination of genistein with primary tumor irradiation is a more effective and safer therapeutic approach as the tumor growth and progression are inhibited both in the primary and metastatic sites

Tyrosine Phosphorylation Allows Integration of Multiple Signaling Inputs by IKKβ

<div><p>Signaling regulated by NFκB and related transcription factors is centrally important to many inflammatory and autoimmune diseases, cancer, and stress responses. The kinase that directly regulates the canonical NFκB transcriptional pathway, Inhibitor of κB kinase β (IKKβ), undergoes activation by Ser phosphorylation mediated by NIK or TAK1 in response to inflammatory signals. Using titanium dioxide-based phosphopeptide enrichment (TiO₂)-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), we analyzed IKKβ phosphorylation in human HEK293 cells expressing IKKβ and FGFR2, a Receptor tyrosine kinase (RTK) essential for embryonic differentiation and dysregulated in several cancers. We attained unusually high coverage of IKKβ, identifying an abundant site of Tyr phosphorylation at Tyr169 within the Activation Loop. The phosphomimic at this site confers a level of kinase activation and NFκB nuclear localization exceeding the iconic mutant S177E/S181E, demonstrating that RTK-mediated Tyr phosphorylation of IKKβ has the potential to directly regulate NFκB transcriptional activation. </p> </div

FGFR2 interacts with IKKβ and stimulates tyrosine phosphorylation of IKKβ.

<p>FGFR2 wildtype (WT) or kinase dead (KD) and IKKβ were expressed in HEK293 cells. (<b>A</b>) <b>FGFR2 associates with IKKβ</b>. IKKβ was immunoprecipitated from lysates and analysed for FGFR2 by immunoblot (top panel). The membrane was stripped and reprobed for IKKβ (second panel). Expression of FGFR2 and IKKβ is shown in cell lysates (lower panels). (<b>B</b>) <b>IKKβ associates with FGFR2</b>. FGFR2 was immunoprecipitated from lysates and analysed for IKKβ by immunoblot (top panel). The membrane was stripped and reprobed for FGFR2 (second panel). Lysate blots are as in (A). (<b>C</b>) <b>FGFR2 and IKKβ are present in complexes with IKKγ/NEMO</b>. Endogenous IKKγ/NEMO was immunoprecipitated from cell lysates expressing FGFR2 and IKKβ using IKKγ/NEMO antisera. The interaction with FGFR2 (top panel) and IKKβ (second panel) was detected by immunoblot. Negative IgG control shown in lane 4B. Note that the 1^st and 2^nd panels represent duplicate gels of the same samples. The thin black lines on the 2^nd panel indicate where additional IgG controls were run but removed from the final figure except for Lane 4B. All samples on this panel are from the same exposure of the same immunoblot. Expression of FGFR2 and IKKβ shown in total lysate (lower panels). (<b>D</b>) <b>FGFR2 stimulates tyrosine phosphorylation of IKKβ</b>. IKKβ was immunoprecipitated from lysates and analysed by phophotyrosine immunoblot (top panel). The membrane was stripped and reprobed for IKKβ (second panel). Expression of FGFR2 derivatives and IKKβ is shown in total lysates (lower panels). The arrow in Lane 5 of the upper panel indicates IKKβ.</p

Composite analysis of mutations of phospho-acceptor sites within the

<p>IKKβ <b><i>Acitvation </i></b><b><i>Loop</i></b>. (<b>A</b>) <b>Contribution of Tyr169, Ser177, Thr180, and Ser181 to IKKβ kinase activation</b>. All possible combinations of single and double mutations were constructed in the IKKβ Activation Loop phospho-acceptor sites, Ser177 and Ser 181, identified previously [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084497#B24" target="_blank">24</a>], and Tyr169 and Thr180 identified in this work. Immunoprecipitated IKKγ/NEMO complexes from HEK293 cells were assayed for <i>in </i><i>vitro</i> kinase activity against the substrate GST-IκBα^(1-54) (top panel), and IKKβ expression is shown (lower panel). (<b>B</b>) <b>Requirement for multiple hydroxyl amino acids within Activation Loop</b>. Multiple mutations within the Activation Loop probe minimal requirements for activation. Mutations were constructed within the Activation Loop phospho-acceptor sites to examine whether Y169E could provide activation when combined with the mutations S177A, T180A, and S181A (compare Lanes 3 and 4). Similarly, Lanes 5 and 6 examine the ability of the “EE” mutations S177E/S181E to provide activation when combined with Y169F and T180A. IKKγ/NEMO immunoprecipiates were examined for <i>in </i><i>vitro</i> kinase activity against the substrate GST-IκBα^(1-54) (top panel). IKKβ expression is shown (lower panel). (<b>C</b>) <b>Y169E stimulates S177/S181 phosphorylation</b>. Activation Loop phosphorylation detected using phospho-S177/S181 antiserum. The ability of IKKβ WT and Y169F to stimulate phosphorylation of S177/S181 as detected by phospho-specific immunoblotting is presented, in comparison with the lack of activity shown by the S177E/S181E “EE” and Y169F mutants. IKKβ expression is shown (lower panel). </p