Alessandra Insinga

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The p53 tumor suppressor belongs to a family of proteins that sense multiple cellular inputs to regulate cell proliferation, apoptosis, and differentiation. Whether and how these functions of p53 intersect with the activity of extracellular growth factors is not understood. Here, we report that key cellular responses to TGF-beta signals rely on p53 family(More)
PURPOSE To describe the clinical management of ovarian stromal cell tumors, which are a heterogeneous group of neoplasms that develop from the sex cords and the ovarian stroma. DESIGN We reviewed the current evidence on the clinical management of these relatively rare ovarian malignancies, which are typically detected at an early stage and may recur as(More)
Histone deacetylases (HDACs) regulate transcription and specific cellular functions, such as tumor suppression by p53, and are frequently altered in cancer. Inhibitors of HDACs (HDACIs) possess antitumor activity and are well tolerated, supporting the idea that their use might develop as a specific strategy for cancer treatment. The molecular basis for(More)
Mutations of p53 are remarkably rare in acute promyelocytic leukemias (APLs). Here, we demonstrate that the APL-associated fusion proteins PML-RAR and PLZF-RAR directly inhibit p53, allowing leukemic blasts to evade p53-dependent cancer surveillance pathways. PML-RAR causes deacetylation and degradation of p53, resulting in repression of p53 transcriptional(More)
Leukemia-associated fusion proteins establish aberrant transcriptional programs, which result in the block of hematopoietic differentiation, a prominent feature of the leukemic phenotype. The dissection of the mechanisms of deregulated transcription by leukemia fusion proteins is therefore critical for the design of tailored antileukemic strategies, aimed(More)
Acute promyelocytic leukemia (APL) is associated with chromosomal translocations resulting in fusion proteins of the retinoic acid receptor (RAR). Here, we report a novel murine model system for APL, based on the transduction of purified murine hematopoietic progenitors (lin(-)) using high-titer retroviral vectors encoding promyelocytic leukemia-RAR(More)
Among the hundreds of oncogenes and tumor suppressors that have been identified in the past 50 years, p53 is probably the best characterized; nevertheless, new functions are constantly being discovered. As a tumor suppressor, p53 regulates cellular responses to different stress stimuli by inducing reversible cell cycle arrest and DNA repair, or triggering(More)
Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral(More)
Histone deacetylases (HDACs) regulate transcription and specific functions, such as tumor suppression by p53, and are frequently altered in cancer. Inhibitors of HDACs (HDACI) possess anti-tumor activity and are well tolerated, suggesting that they might develop into a specific strategy for cancer treatment. Indeed, HDACIs have successfully entered clinical(More)
DNA damage leads to a halt in proliferation owing to apoptosis or senescence, which prevents transmission of DNA alterations. This cellular response depends on the tumor suppressor p53 and functions as a powerful barrier to tumor development. Adult stem cells are resistant to DNA damage-induced apoptosis or senescence, however, and how they execute this(More)