p62 and PAR-4 as regulators of PKCζ : molecular interactions and specific cleavages = PKCζ 의 조절인자로서의 p62와 PAR-4 : 분자간의 상호결합과 특이적인 절단현상molecular interactions and specific cleavages

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It has been reported that PAR-4 binds to and inhibits PKCζ that ultimately suppresses NFκB activation, while p62 binds to and recruits PKCζ to the NFκB signaling complex for activation of IKKβ and NFκB. As cells express both PAR-4 and p62, a mechanism to coordinate the binding proteins for PKCζ regulation is expected to exist. The present data show that p62 and PAR-4 directly interact each other and form a ternary complex with PKCζ. Furthermore, p62 not only enhances the catalytic activity of PKCζ but also reactivates the catalytically inactive PKCζ caused by PAR-4 binding. As the result, over-expression of p62 protects cells from PAR-4-mediated inactivation of NFκB and apoptotic death. Thus, the regulatory role of p62 for PKCζ is important in activation of NFκB and ultimately, in survival of cells which expresses PAR-4 constitutively. Interestingly, both PAR-4 and p62 are cleaved by caspases during apoptosis. Cleavage analysis using specific inhibitors for caspases shows that caspase-6 and -1/8 cleave p62 and alternatively, PAR-4 is cleaved by caspase-6. In addition, study with the site specific mutants of p62 and PAR-4 revealed that caspase-6 cleaved Asp(133) residue of PAR-4 and Asp(256) residue of p62, and caspase-1/8 cleaved another site of p62, Asp(329). The physiological role of these cleavages of the two protein is not clear, but the alteration of the ternary complex by caspase-mediated cleavages during apoptosis might contribute to apoptosis positively.
Advisors
Kim, Jeong-HoeresearcherShin, Jae-Kyoonresearcher김정회researcher신재균researcher
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
2002
Identifier
174545/325007 / 000975333
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생물과학과, 2002.2, [ ix. 93 p. ]

Keywords

PAR-4; PKC; cleavage; 상호결합; 절단현상; p62; 조절인자

URI
http://hdl.handle.net/10203/27516
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=174545&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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