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
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0429-2.pdf

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
Commentator:洪建中老師
Time:2011/4/29,16:00-16:50
Place:602
 
Background:
  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
Objective:
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.
Results:
  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.
Conclusion:
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.
 
References:
Nateri, A. S., Riera-Sans, L., Da Costa, C. & Behrens, A. The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science 303, 1374–1378 (2004).