American Association for Cancer Research
Browse
00085472can172314-sup-187164_3_supp_4597778_p4pg14.pdf (555.95 kB)

Figure S1 from Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis

Download (555.95 kB)
journal contribution
posted on 2023-03-31, 01:22 authored by Chao Huang, Zhe Zhang, Lihan Chen, Hank W. Lee, Marina K. Ayrapetov, Ting C. Zhao, Yimei Hao, Jinsong Gao, Chunzhang Yang, Gautam U. Mehta, Zhengping Zhuang, Xiaoren Zhang, Guohong Hu, Y. Eugene Chin

Interaction between Src and CBP

Funding

National Natural Science Foundation of China

Ministry of Science and Technology of China

History

ARTICLE ABSTRACT

Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src–cell membrane association–dissociation and catalytic activation–inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation.Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825–38. ©2018 AACR.