UNDERSTANDING THE MOLECULAR MECHANISMS CONTROLLING NUCLEOLAR SURVEILLANCE IN DISEASE

Grant number: 1102609 | Funding period: 2016 - 2019

Completed

Abstract

Alterations in the ability of cells to make ribosomes, the cellular factories that make protein, contribute to a range of diseases including cancer and a class of inherited disorders called ribosomopathies that are rare but largely untreatable. These changes cause disease by controlling the “nucleolar surveillance pathway” that causes cells to either stop dividing or die. Here we propose to identify new genes that regulate this pathway to identify new targets for treating these diseases.

Related publications (3)

Scholarly works icon

Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway

Katherine M Hannan, Priscilla Soo, Mei S Wong, Justine K Lee, Nadine Hein, Perlita Poh, Kira D Wysoke, Tobias D Williams, Christian Montellese, Lorey K Smith, Sheren J Al-Obaidi, Lorena Nunez-Villacis, Megan Pavy, Jin-Shu He, Kate M Parsons, Karagh E Loring, Tess Morrison, Jeannine Diesch, Gaetan Burgio, Rita Ferreira

2022-11-01

The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal..

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Impaired ribosome biogenesis checkpoint activation induces p53-dependent MCL-1 degradation and MYC-driven lymphoma death

Ana Domostegui, Suresh Peddigari, Carol A Mercer, Flavia Iannizzotto, Marta L Rodriguez, Marta Garcia-Cajide, Virginia Amador, Sarah T Diepstraten, Gemma L Kelly, Ramon Salazar, Sara C Kozma, Eric P Kusnadi, Jian Kang, Antonio Gentilella, Richard B Pearson, George Thomas, Joffrey Pelletier

2021-06-17

MYC-driven B-cell lymphomas are addicted to increased levels of ribosome biogenesis (RiBi), offering the potential for therapeutic..

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Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis

Eric P Kusnadi, Anna S Trigos, Carleen Cullinane, David L Goode, Ola Larsson, Jennifer R Devlin, Keefe T Chan, David P De Souza, Malcolm J McConville, Grant A McArthur, George Thomas, Elaine Sanij, Gretchen Poortinga, Ross D Hannan, Katherine M Hannan, Jian Kang, Richard B Pearson

2020-11-02

Elevated ribosome biogenesis in oncogene-driven cancers is commonly targeted by DNA-damaging cytotoxic drugs. Our previous first-i..