Supplementary table 1 and 2 from Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1

Ann, Eun-Jung; Kim, Mi-Yeon; Yoon, Ji-Hye; Ahn, Ji-Seon; Jo, Eun-Hye; Lee, Hye-Jin; Lee, Hyun-Woo; Kang, Hyeok-Gu; Choi, Dong Wook; Chun, Kyung-Hee; Lee, Ji Shin; Choi, Cheol Yong; Ferrando, Adolfo A.; Lee, Keesook; Park, Hee-Sae

doi:10.1158/0008-5472.22411064.v1

00085472can153310-sup-159092_2_supp_3527607_988hpl.docx (46.39 kB)

Supplementary table 1 and 2 from Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1

journal contribution

posted on 2023-03-31, 00:05 authored by Eun-Jung Ann, Mi-Yeon Kim, Ji-Hye Yoon, Ji-Seon Ahn, Eun-Hye Jo, Hye-Jin Lee, Hyun-Woo Lee, Hyeok-Gu Kang, Dong Wook Choi, Kyung-Hee Chun, Ji Shin Lee, Cheol Yong Choi, Adolfo A. Ferrando, Keesook Lee, Hee-Sae Park

Supplementary Table S1: Immunohistochemical staining of Notch1-IC and HIPK2 in serial tissue arrays of 61 breast cancer samples. Supplementary Table S2: Semi-Quantitative analysis of Notch1-IC, phosphorylated Notch1-IC T2512, HIPK2, and Fbw7 expression in breast cancer tissues.

Funding

NRF

Ministry of Science

ICT and Future Planning

History

ARTICLE ABSTRACT

The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728–40. ©2016 AACR.