Identification of a co-activator that links growth factor signalling to c-Jun/AP-1 activation (Nat Cell Biol, 2010, 12:963-972)

報告日期: 2011/04/29
報告時間: 16:00/16:50
報告學生: 嚴佳冠
講評老師: 洪建中

Full Text:

Identification of a co-activator that links growth factor signalling to c‑Jun/AP‑1 activation
Clare C. Davies, Atanu Chakraborty, Filippo Cipriani1, Katharina Haigh, Jody J. Haigh and Axel Behrens
nature cell biology,2010,12:963-973
Speaker: 嚴佳冠
  The proto-oncoprotein c‑Jun belongs to the dimeric AP‑1 family of tran­scription factors, which are important regulators of cellular prolifera­tion, apoptosis and tumorigenesis1–3. AP‑1 activity is strongly induced in response to numerous signals, including growth factors, cytokines and extracellular stress
The AP‑1 transcription factor c‑Jun is essential for cellular proliferation in many cell types, but the molecular link between growth factors and c‑Jun activation has been enigmatic.
  In this study they identify a RING-domain containing protein, which they have named RACO‑1, as a c‑Jun co-activator that is regulated by the MEK signalling pathway. Thus RACO‑1 is a molecular link between growth factor signalling and AP‑1 activation.
In unstimulated conditions, auto-ubiquitylation of RACO-1 promotes the formation of a degradative poly-ubiquitin chain onto C-terminal lysine residues. In response to growth factor induced activation of the MEK-ERK signalling pathway, an unidentified RACO-1 E3 ligase induces the formation of a K63-linked ubiquitin chains that blocks degradative auto-ubiquitylation leading to the stabilisation of RACO-1 protein levels.
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