The Nucleolus under Stress

Abstract

Cells typically respond quickly to stress, altering their metabolism to compensate. In mammalian cells, stress signaling usually leads to either cell-cycle arrest or apoptosis, depending on the severity of the insult and the ability of the cell to recover. Stress also often leads to reorganization of nuclear architecture, reflecting the simultaneous inhibition of major nuclear pathways (e.g., replication and transcription) and activation of specific stress responses (e.g., DNA repair). In this review, we focus on how two nuclear organelles, the nucleolus and the Cajal body, respond to stress. The nucleolus senses stress and is a central hub for coordinating the stress response. We review nucleolar function in the stress-induced regulation of p53 and the specific changes in nucleolar morphology and composition that occur upon stress. Crosstalk between nucleoli and CBs is also discussed in the context of stress responses.

The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway

“…The placticity and highly dynamic nature of the nucleolar proteome is a major determinant of decoding a stress signal to a signaling output 23 . The changes in the nucleolar proteome upon stress conditions are directly linked to the regulation of key components of the cell cycle 23,29 .…”

“…The placticity and highly dynamic nature of the nucleolar proteome is a major determinant of decoding a stress signal to a signaling output 23 . The changes in the nucleolar proteome upon stress conditions are directly linked to the regulation of key components of the cell cycle 23,29 . To our knowledge MLN4924 is the first example of a small compound that re-organises the nucleolar proteome and activates p53 with all the characteristics of "nucleolar stress" in the absence of inhibition of nucleolar transcription.…”

“…Changes in the nucleolar morphology usually reflect changes in the nucleolar function, which are detected by multiple cell cycle regulators 23 . The p53 tumour suppressor is a sensitive sensor of nucleolar misfunction.…”

“…What is also evident is that the nucleolus is not a static subnuclear structure but responds to a great variety of cellular stresses. DNA damage induced by ionizing radiation, UV or chemotherapeutic drugs, inhibition of RNA Pol I transcription by nutrient starvation or Actinomycin D (ActD), proteasome inhibition and viral infection, can all change nucleolar structure and alter the nucleolar proteome 18,19,20,21,22,23 .…”

Gold nanoparticles induce nuclear damage in breast cancer cells, which is further amplified by hyperthermia

“…Nucleoli are specialized compartments in the nucleus that transcribe ribosomal RNA genes and assemble ribosomal subunits [21,22]. Nucleolar hypertrophy is a hallmark of proliferating cancer cells and has been demonstrated especially in breast cancer tissue and cells [23][24][25][26][27][28].…”