Connecting the nucleolus to the cell cycle and human disease.
Long known as the center of ribosome synthesis, the nucleolus is connected to cell cycle regulation in more subtle ways. One is a surveillance system that reacts promptly when rRNA synthesis or processing is impaired, halting cell cycle progression. Conversely, the nucleolus also acts as a first-responder to growth-related stress signals. Here we review emerging concepts on how these "infraribosomal" links between the nucleolus and cell cycle progression operate in both forward and reverse gears. We offer perspectives on how new cancer therapeutic designs that target this infraribosomal mode of cell growth control may shape future clinical progress.
Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas, USA; and rtsai@ibt.tamhsc.edu thoru.pederson@umassmed.edu.
Robert Y L
RY
Tsai
Program in Cell and Developmental Dynamics, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA rtsai@ibt.tamhsc.edu thoru.pederson@umassmed.edu.
Thoru
T
Pederson
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000502:physiology*; D002466:Cell Nucleolus / Q000502:physiology*; D004260:DNA Repair; D005544:Forecasting; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000502:physiology; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins
cancer; cell cycle; ribosome synthesis