Notch-Induced E2A Degradation Requires CHIP and Hsc70 as Novel Facilitators of Ubiquitination

• DOI: 10.1128/mcb.24.20.8951-8962.2004
• Publication Date: 2004-09-29T02:17:34Z
• Authors: Zhong Huang; Lei Nie; Min Xu; Xiao-Hong Sun
• Keywords: Degradation

AbstractE2A transcription factors, E12 and E47, are important regulators of lymphocyte development. Notch signaling pathways have been shown to regulate E2A function by accelerating the degradation proteins through a mitogen-activated protein kinase-dependent ubiquitin-mediated pathway. To further understand mechanism underlying ubiquitination degradation, we conducted yeast two-hybrid screen identified carboxyl terminus Hsc70-interacting (CHIP) as an E47 binding protein. Here, show that CHIP associates with in vivo overexpression induces phosphorylation-dependent manner. Conversely, knocking down small interfering RNA alleviates Notch-induced degradation. binds E homology domains 2 3 (EHD2 EHD3). This interaction between is independent U-box domain E3 ubiquitin ligase activity but requires chaperone tetratricopeptide repeats domain. The ability induce correlates its bind E47. We propose CHIP, together partner Hsc70, forms preubiquitination complex (PUC) Skp2, thus facilitating Skp2. also Cul1, which introduces PUC SCF complex, responsible for ubiquitination. Therefore, plays crucial role proteins. acknowledge Stuart Robinson participating library summer research student. grateful S. Scott Perry Darryll Dudley critical reading manuscript.The work was supported grants from National Institutes Health X.-H.S. (AI33597, CA77553, AI056129, RR15577 [COBRE award]). Z.H. funded training grant 1T32-AI07633-01A1 Institute Allergy Infectious Diseases.