Unknown,Transcriptomics,Genomics,Proteomics

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Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals

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: (i) The first pulse induces essential metabolic enzymes and activates p53-dependent restraining processes. (ii) The second pulse eliminates, via the PI3K/AKT pathway, the suppressive action of p53, as well as (iii) 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 novel gating mechanisms, which ensure that cells ignore fortuitous growth factors, and undergo proliferation only in response to consistent mitogenic signals. 17 samples; one control sample, time zero.

ORGANISM(S): Homo sapiens

SUBMITTER: Yotam Drier

PROVIDER: E-GEOD-27629 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

Zwang Yaara Y Sas-Chen Aldema A Drier Yotam Y Shay Tal T Avraham Roi R Lauriola Mattia M Shema Efrat E Lidor-Nili Efrat E Jacob-Hirsch Jasmine J Amariglio Ninette N Lu Yiling Y Mills Gordon B GB Rechavi Gideon G Oren Moshe M Domany Eytan E Yarden Yosef Y

Molecular cell 20110501 4

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: ( ...[more]

PMID: 21596316

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Dataset Information

Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals

Publications

Two phases of mitogenic signaling unveil roles for p53 and EGR1 in elimination of inconsistent growth signals.

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