Oncotarget

Research Papers:

HAX1 regulates E3 ubiquitin ligase activity of cIAPs by promoting their dimerization

Jin Sun Choi _, Byoung Chul Park, Seung Wook Chi, Kwang-Hee Bae, Sunhong Kim, Sayeon Cho, Woo-Chan Son, Pyung Keun Myung, Jeong-Hoon Kim and Sung Goo Park

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:10084-10099. https://doi.org/10.18632/oncotarget.2459

Metrics: PDF 2241 views  |   HTML 1758 views  |   ?  


Abstract

Jin Sun Choi1,8, Byoung Chul Park1, Seung Wook Chi1, Kwang-Hee Bae2, Sunhong Kim3,10, Sayeon Cho5, Woo-Chan Son6,7, Pyung Keun Myung8, Jeong-Hoon Kim4,9, Sung Goo Park1

1 Medical Proteomics Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea

2 Cell Function Regulation Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea

3 Targeted Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea

4 Targeted Gene Regulation Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon, Republic of Korea

5College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea

6Asan Institute for Life Sciences and Asan Medical Center, Seoul, Republic of Korea

7Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea

8College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea

9Department of Functional Genomics, Daejeon, Republic of Korea

10Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Republic of Korea

Correspondence to:

Dr. Sung Goo Park, e-mail: sgpark@kribb.re.kr

Dr. Jeong-Hoon Kim, e-mail: jhoonkim@kribb.re.kr

Received: June 16, 2014     Accepted: September 06, 2014     Published: September 29, 2014

ABSTRACT

HS-1-associated protein X-1 (HAX1) is a multi-functional protein which was first identified as a Hematopoietic cell specific Lyn Substrate 1 (HS1)-binding protein. Although the roles of HAX1 in apoptosis have been unraveled and HAX1 has been proposed to be involved in several diseases, additional roles of HAX1 are still being identified. Here, we demonstrated that HAX1 directly interacted with cellular Inhibitor of Apoptosis Proteins (cIAPs), ubiquitin E3 ligases which regulate the abundance of cellular proteins, via ubiquitin-dependent proteasomal degradation. We showed that HAX1 promotes auto-ubiquitination and degradation of cIAPs by facilitating the intermolecular homodimerization of RING finger domain. Moreover, HAX1 regulates the non-canonical Nuclear Factor-κB (NF-κB) signaling pathway by modulating the stability of NF-κB-Inducing Kinase (NIK), which is one of the substrates of cIAPs. Taken together, these results unveil a novel role of HAX1 in the non-canonical NF-κB pathway, and provide an important clue that HAX1 is a potential therapeutic target for the treatment of cancer.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 2459