YB-1 is important for late-stage embryonic development, optimal cellular stress responses, and the prevention of premature senescence.
Proteins containing "cold shock" domains belong to the most evolutionarily conserved family of nucleic acid-binding proteins known among bacteria, plants, and animals. One of these proteins, YB-1, is widely expressed throughout development and has been implicated as a cell survival factor that regulates the transcription and/or translation of many cellular growth and death-related genes. For these reasons, YB-1 deficiency has been predicted to be incompatible with cell survival. However, the majority of YB-1(-/-) embryos develop normally up to embryonic day 13.5 (E13.5). After E13.5, YB-1(-/-) embryos exhibit severe growth retardation and progressive mortality, revealing a nonredundant role of YB-1 in late embryonic development. Fibroblasts derived from YB-1(-/-) embryos displayed a normal rate of protein synthesis and minimal alterations in the transcriptome and proteome but demonstrated reduced abilities to respond to oxidative, genotoxic, and oncogene-induced stresses. YB-1(-/-) cells under oxidative stress expressed high levels of the G(1)-specific CDK inhibitors p16Ink4a and p21Cip1 and senesced prematurely; this defect was corrected by knocking down CDK inhibitor levels with specific small interfering RNAs. These data suggest that YB-1 normally represses the transcription of CDK inhibitors, making it an important component of the cellular stress response signaling pathway.
Lu
Zhi Hong
ZH
Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Books
Jason T
JT
Ley
Timothy J
TJ
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000166:cytology; D047108:Embryonic Development; D005317:Fetal Growth Retardation / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018390:Gene Targeting; D005804:Genes, Lethal; D051379:Mice; D018384:Oxidative Stress; D014176:Protein Biosynthesis / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins; C493957:Cdkn1a protein, mouse; C541744:Ybx1 protein, mouse; D014157:Transcription Factors