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 gene sets
      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

(show 397 gene sets from the same authors)
External links  
Organism Homo sapiens
Contributed by Yaara Zwang (Broad Institute)
Source platform HuGene-1_0_st
Dataset references (show 1 datasets)
Compendia expression profiles Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Show members (show 406 members mapped to 312 genes)
Version history 3.1: First introduced
