Interleukin-32 alpha modulates promyelocytic leukemia zinc finger gene activity by inhibiting protein kinase C epsilon-dependent sumoylation
- Authors
- Park, Yun Sun; Kang, Jeong-Woo; Lee, Dong Hun; Kim, Man Sub; Bak, Yesol; Yang, Young; Lee, Hee-Gu; Hong, Jintae; Yoon, Do-Young
- Issue Date
- Oct-2014
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Interleukin 32 alpha; Promyelocytic leukemia zinc finger protein; Small ubiquitin-like modifier-2
- Citation
- INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v.55, pp 136 - 143
- Pages
- 8
- Journal Title
- INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
- Volume
- 55
- Start Page
- 136
- End Page
- 143
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10783
- DOI
- 10.1016/j.biocel.2014.08.018
- ISSN
- 1357-2725
1878-5875
- Abstract
- Interleukin-32 (IL-32) is a proinflammatory cytokine. However, there is growing evidence that IL-32 also plays a mediatory role intracellularly. In this study, we present evidence that IL-32 alpha modifies and inhibits promyelocytic leukemia zinc finger (PLZF), a sequence-specific transcriptional regulator that regulates the expression of a subset of interferon (IFN)-stimulated genes (ISGs). We screened IL-32 alpha-interacting proteins in a human spleen cDNA library using the yeast two-hybrid assay, and investigated the functional relevance of the interaction between IL-32 alpha and PLZF. We demonstrated that IL-32 alpha interacts with protein kinase C (PKC)delta and PKC epsilon in a phorbol 12-myristate 13-acetate (PMA) dependent way, and that PKC epsilon regulates the interaction of IL-32 alpha with PLZF. We verified the involvement of PKC epsilon in the interaction between these proteins by using various PKC inhibitors. PLZF is known to be modified by small ubiquitin-like modifier (SUMO)-1, but it is unclear whether SUMO-2 conjugation of PLZF occurs. We showed that IL-32 alpha inhibited SUMO-2-conjugation of PLZF. Further, we demonstrated that sumoylated PLZF decreased when IL-32 alpha was co-expressed. PKC epsilon affected the sumoylation of PLZF only in the presence of IL-32 alpha because PKC inhibitor treatment did not reduce PLZF sumoylation in the absence of IL-32 alpha. We finally investigated whether IL-32 alpha-mediated inhibition of PLZF sumoylation affected the transcriptional activity of PLZF, and demonstrated that the inhibition of sumoylation of PLZF by IL-32 alpha down-regulated ISGs induced by PLZF. Together, our data suggest that IL-32 alpha associates with PLZF and PKC epsilon, and then inhibits PLZF sumoylation, resulting in suppression of the transcriptional activity of PLZF. (C) 2014 Elsevier Ltd. All rights reserved.
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