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Heat-shock Protein 90 Controls the Expression of Cell-cycle Genes by Stabilizing Metazoan-specific Host-cell Factor HCFC1
Abstract: Molecular chaperones such as heat-shock proteins (HSPs) help in protein folding. Their function in the cytosol has been well studied. Notably, chaperones are also present in the nucleus, a compartment where proteins enter after completing de novo folding in the cytosol, and this raises an important question about chaperone function in the nucleus. We performed a systematic analysis of the nuclear pool of heat-shock protein 90. Three orthogonal and independent analyses led us to the core functional interactome of HSP90. Computational and biochemical analyses identify host cell factor C1 (HCFC1) as a transcriptional regulator that depends on HSP90 for its stability. HSP90 was required to maintain the expression of HCFC1-targeted cell-cycle genes. The regulatory nexus between HSP90 and the HCFC1 module identified in this study sheds light on the relevance of chaperones in the transcription of cell-cycle genes. Our study also suggests a therapeutic avenue of combining chaperone and transcription inhibitors for cancer treatment
Stress-induced Nuclear Condensation of NELF Drives Transcriptional Downregulation
Abstract: In response to stress, human cells coordinately downregulate transcription and translation of housekeeping genes. To downregulate transcription, the negative elongation factor (NELF) is recruited to gene promoters impairing RNA polymerase II elongation. Here we report that NELF rapidly forms nuclear condensates upon stress in human cells. Condensate formation requires NELF dephosphorylation and SUMOylation induced by stress. The intrinsically disordered region (IDR) in NELFA is necessary for nuclear NELF condensation and can be functionally replaced by the IDR of FUS or EWSR1 protein. We find that biomolecular condensation facilitates enhanced recruitment of NELF to promoters upon stress to drive transcriptional downregulation. Importantly, NELF condensation is required for cellular viability under stressful conditions. We propose that stress-induced NELF condensates reported here are nuclear counterparts of cytosolic stress granules. These two stress-inducible condensates may drive the coordinated downregulation of transcription and translation, likely forming a critical node of the stress survival strategy
Fernando García
None
Quantitative Real-time In-cell Imaging Reveals Heterogeneous Clusters of Proteins Prior to Condensation
Abstract: Our current understanding of biomolecular condensate formation is largely based on observing the final near-equilibrium condensate state. Despite expectations from classical nucleation theory, pre-critical protein clusters were recently shown to form under subsaturation conditions in vitro; if similar long-lived clusters comprising more than a few molecules are also present in cells, our understanding of the physical basis of biological phase separation may fundamentally change. Here, we combine fluorescence microscopy with photobleaching analysis to quantify the formation of clusters of NELF proteins in living, stressed cells. We categorise small and large clusters based on their dynamics and their response to p38 kinase inhibition. We find a broad distribution of pre-condensate cluster sizes and show that NELF protein cluster formation can be explained as non-classical nucleation with a surprisingly flat free-energy landscape for a wide range of sizes and an inhibition of condensation in unstressed cells
A Nation for All
Argues that racism and antiracism continue to coexist in Cuban nationalism and society despite its fight for freedom, and describes the limitations Afro-Cubans face in job access, education, and political representation.
A Nation for All
After thirty years of anticolonial struggle against Spain and four years of military occupation by the United States, Cuba formally became an independent republic in 1902. The nationalist coalition that fought for Cuba's freedom, a movement in which blacks and mulattoes were well represented, had envisioned an egalitarian and inclusive country--a nation for all, as Jose Marti described it. But did the Cuban republic, and later the Cuban revolution, live up to these expectations? Tracing the formation and reformulation of nationalist ideologies, government policies, and different forms of social and political mobilization in republican and postrevolutionary Cuba, Alejandro de la Fuente explores the opportunities and limitations that Afro-Cubans experienced in such areas as job access, education, and political representation. Challenging assumptions of both underlying racism and racial democracy, he contends that racism and antiracism coexisted within Cuban nationalism and, in turn, Cuban society. This coexistence has persisted to this day, despite significant efforts by the revolutionary government to improve the lot of the poor and build a nation that was truly for all.
Terranova
Terranova is the story of Spain s twentieth-century industrial cod fishery on the Grand Banks of Newfoundland. It combines oral history (including interviews with over 300 participants in the fishery) with socio-political-economic history to describe how the industry and Spain itself evolved over seven decades. Terranova pays special attention to how work and life onboard trawlers changed in 1926, when Spain s industrial fishery began, and how they have evolved through the turn of the twenty-first century. It concludes by describing how technological advances and increased competition among fishers brought the collapse of the Newfoundland cod fishery in 1992.
Jews and Muslims Made Visible in Christian Iberia and Beyond, 14th to 18th Centuries
This volume aims to show through various case studies how the interrelations between Jews, Muslims and Christians in Iberia were negotiated in the field of images, objects and architecture during the Later Middle Ages and Early Modernity.
Rural Progress, Rural Decay
* Profiles Ecuador as a broadly applicable case study to explore grassroots development initiatives * Stresses how macroeconomic conditions must change to achieve equitable development How do rural development programs, especially those run by nongovernmental organizations, contend with the forces of structural adjustment programs and economic liberalization? Rural Progress, Rural Decay asserts that NGOs make little progress in promoting equitable development and "poor people’s entrepreneurship" in an economic and political environment dominated by big business. The editors probe the adverse consequences of neoliberal macroeconomic policies on development in low-income countries. This illuminating study is a necessary read for those interested in local communities in Latin America and other parts of the developing world.
