Human Gene Set: ZWANG_DOWN_BY_2ND_EGF_PULSE


Standard name ZWANG_DOWN_BY_2ND_EGF_PULSE
Systematic name M2615
Brief description Genes down-regulated by second pulse of EGF [GeneID=1950] in 184A1 cells (mammary epithelium).
Full description or abstract Normal cells require continuous exposure to growth factors in order to cross a restriction point and commit to cell-cycle progression. This can be replaced by two short, appropriately spaced pulses of growth factors, where the first pulse primes a process, which is completed by the second pulse, and enables restriction point crossing. Through integration of comprehensive proteomic and transcriptomic analyses of each pulse, we identified three processes that regulate restriction point crossing: (1) The first pulse induces essential metabolic enzymes and activates p53-dependent restraining processes. (2) The second pulse eliminates, via the PI3K/AKT pathway, the suppressive action of p53, as well as (3) sets an ERK-EGR1 threshold mechanism, which digitizes graded external signals into an all-or-none decision obligatory for S phase entry. Together, our findings uncover two gating mechanisms, which ensure that cells ignore fortuitous growth factors and undergo proliferation only in response to consistent mitogenic signals.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 21596316   Authors: Zwang Y,Sas-Chen A,Drier Y,Shay T,Avraham R,Lauriola M,Shema E,Lidor-Nili E,Jacob-Hirsch J,Amariglio N,Lu Y,Mills GB,Rechavi G,Oren M,Domany E,Yarden Y
Exact source Table 2S: Down-regulated by 2nd pulse
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Source species Homo sapiens
Contributed by Yaara Zwang (Broad Institute)
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identifier namespace		 AFFY_HuGene
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Version history 3.1: First introduced

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