Mariangela Rossi

Publications (5)24.4 Total impact

• Source

  Available from: Viola Calabrò

  Article: MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation.

  Francesco Galli, Mariangela Rossi, Yuri D'Alessandra, Marco De Simone, Teresa Lopardo, Ygal Haupt, Osnat Alsheich-Bartok, Shira Anzi, Eitan Shaulian, Viola Calabrò, Girolama La Mantia, Luisa Guerrini
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  ABSTRACT: Tight control of p63 protein levels must be achieved under differentiation or apoptotic conditions. Here, we describe a new regulatory pathway for the DeltaNp63alpha protein. We found that MDM2 binds DeltaNp63alpha in the nucleus promoting its translocation to the cytoplasm. The MDM2 nuclear localization signal is required for DeltaNp63alpha nuclear export and subsequent degradation, whereas the MDM2 ring-finger domain is dispensable. Once exported to the cytoplasm by MDM2, p63 is targeted for degradation by the Fbw7 E3-ubiquitin ligase. Efficient degradation of DeltaNp63alpha by Fbw7 (also known as FBXW7) requires GSK3 kinase activity. By deletion and point mutations analysis we have identified a phosphodegron located in the alpha and beta tail of p63 that is required for degradation. Furthermore, we show that MDM2 or Fbw7 depletion inhibits degradation of endogenous DeltaNp63alpha in cells exposed to UV irradiation, adriamycin and upon keratinocyte differentiation. Our findings suggest that following DNA damage and cellular differentiation MDM2 and Fbw7 can cooperate to regulate the levels of the pro-proliferative DeltaNp63alpha protein.
  Journal of Cell Science 07/2010; 123(Pt 14):2423-33. · 6.11 Impact Factor
• Source

  Available from: Viola Calabrò

  Article: Itch/AIP4 associates with and promotes p63 protein degradation.

  Mariangela Rossi, Marco De Simone, Alessandra Pollice, Raffaela Santoro, Girolama La Mantia, Luisa Guerrini, Viola Calabrò
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  ABSTRACT: p63, a protein related to the tumor suppressor p53, is a transcription factor that plays an important role in epidermal differentiation and limb development. The gene has two distinct promoters that allow the formation of proteins that either contain (TA) or lack (DeltaN) a transactivation domain. In addition, alternative splicing at the 3' end generates proteins with different C-termini, denoted alpha, beta and gamma for a total of six isoforms. DeltaNp63alpha isoform is the main isoform expressed at all stages of development, however the relative contribution of individual p63 isoform during ectodermal differentiation and organogenesis is still far from understood. Overexpression of DeltaNp63 led to increased growth of transformed cells in vitro and in vivo while treatment of keratinocytes with ultraviolet irradiation causes downregulation of DeltaNp63 proteins and their corresponding mRNA. The p63 gene locus is often amplified in squamous cell carcinomas while alterations in the relative levels of TA and DeltaNp63 correlate with prognosis in several human cancers suggesting that fine regulation of p63 intracellular levels must be of pivotal importance in controlling cell proliferation, death and differentiation. Despite its relevance little is known on the mechanisms controlling p63 protein levels. Here we show that Itch/AIP4, a HECT E3-ubiquitin ligase, promotes p63 degradation. Using a set of p63 deletion mutants, we have identified a region and two critical lysine residues of p63, associated to human Split-Hand and Foot Malformation-4 (SHFM-4) syndrome, which are involved in the mechanism of Itch-mediated p63 degradation.
  Cell cycle (Georgetown, Tex.) 09/2006; 5(16):1816-22. · 5.36 Impact Factor
• Article: Proteomic analysis of MCF-7 cell lines expressing the zinc-finger or the proline-rich domain of retinoblastoma-interacting-zinc-finger protein.

  Angela Chambery, Annarita Farina, Antimo Di Maro, Mariangela Rossi, Ciro Abbondanza, Bruno Moncharmont, Livia Malorni, Giuseppina Cacace, Gabriella Pocsfalvi, Antonio Malorni, Augusto Parente
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  ABSTRACT: To identify a growth-promoting activity related to retinoblastoma-interacting-zinc-finger (RIZ) protein, differential protein expression of MCF-7 cell lines expressing the zinc-finger or the proline-rich domain of RIZ protein was analyzed by a robust bottom-up mass-spectrometry proteomic approach. Spots corresponding to qualitative and quantitative differences in protein expression have been selected and identified. Some of these proteins have been previously reported as being associated with different types of carcinomas or involved in cell proliferation and differentiation. Knowledge of specific differentially expressed proteins by MCF-7-derived cell lines expressing RIZ different domains will provide the basis for identifying a growth-promoting activity related to RIZ gene products.
  Journal of Proteome Research 06/2006; 5(5):1176-85. · 5.11 Impact Factor
• Article: Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation.

  Patrizia Gazzerro, Ciro Abbondanza, Andrea D'Arcangelo, Mariangela Rossi, Nicola Medici, Bruno Moncharmont, Giovanni Alfredo Puca
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  ABSTRACT: The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression.
  Experimental Cell Research 03/2006; 312(3):340-9. · 3.58 Impact Factor
• Article: The Zn-finger domain of RIZ protein promotes MCF-7 cell proliferation.

  Mariangela Rossi, Ciro Abbondanza, Andrea D'Arcangelo, Patrizia Gazzerro, Nicola Medici, Bruno Moncharmont, Giovanni Alfredo Puca
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  ABSTRACT: In order to understand the oncogenic properties of retinoblastoma-interacting zinc-finger (RIZ) gene products, we produced an MCF-7-derived cell line expressing a fusion protein containing the zinc-finger (aa 359-497) domain of RIZ protein (MCF-7/znf). The Zn-finger domain contains three of the eight putative Zn-finger motifs and is located in proximity of the E1A-like domain containing the Rb protein-binding motif. The MCF-7/znf cells showed a higher growth rate than the parental or the control cell lines, both in hormone-deprived conditions or upon estrogen stimulation. Furthermore, they were less sensitive to the growth inhibitory effect of anti-estrogens and showed a higher level of expression of cyclin D1 and A. The expressed Zn-finger domain recombinant product was localized in the nucleus and in the nucleoli and its expression modified the pattern of actin staining in the cytoplasm. In conclusion the presented results indicated that the Zn-finger domain could be endowed with the putative oncogenic activity of RIZ2 gene product.
  Cancer Letters 12/2004; 215(2):229-37. · 4.24 Impact Factor