Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip

Jongeun Lee, Kwi Hoon Jang, Hakhyun Kim, Younglan Lim, Sujin Kim, Han Na Yoon, In Kwon Chung, Jürgen Roth, Nam-on Ku

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Keratin 8 and 18 (K8/K18) are major intermediate filament proteins of liver hepatocytes. They provide mechanical and nonmechanical stability, thereby protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas-mediated liver cell apoptosis. However, the role of c-Flip protein in K8-null related susceptibility to liver injury is controversial. Here we analyzed c-Flip protein expression in various K8 or K18 null/mutant transgenic livers and show that they are similar in all analyzed transgenic livers and that previously reported c-Flip protein changes are due to antibody cross-reaction with mouse K18. Furthermore, analysis of various apoptosis-or cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-κB and various stress activated protein kinases (SAPKs), such as p38 MAPK, p44/42 MAPK and JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear NF-κB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NFkB and the studied protein kinases are associated with the K8/ K18 complex and are released upon phosphorylation. Therefore, interaction of keratins with cell survival-related protein kinases and transcription factors is another important factor for hepatocyte survival.

Original languageEnglish
Pages (from-to)695-702
Number of pages8
JournalBiology Open
Volume2
Issue number7
DOIs
Publication statusPublished - 2013 Jul 15

Fingerprint

Keratin-8
keratin
Heat-Shock Proteins
mitogen-activated protein kinase
Liver
Protein Kinases
hepatocytes
inactivation
apoptosis
Apoptosis
liver
Hepatocytes
Phosphorylation
protein kinases
cell viability
phosphorylation
genetically modified organisms
intermediate filament proteins
Cell Survival
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lee, Jongeun ; Jang, Kwi Hoon ; Kim, Hakhyun ; Lim, Younglan ; Kim, Sujin ; Yoon, Han Na ; Chung, In Kwon ; Roth, Jürgen ; Ku, Nam-on. / Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip. In: Biology Open. 2013 ; Vol. 2, No. 7. pp. 695-702.
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Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip. / Lee, Jongeun; Jang, Kwi Hoon; Kim, Hakhyun; Lim, Younglan; Kim, Sujin; Yoon, Han Na; Chung, In Kwon; Roth, Jürgen; Ku, Nam-on.

In: Biology Open, Vol. 2, No. 7, 15.07.2013, p. 695-702.

Research output: Contribution to journalArticle

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AU - Lee, Jongeun

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AU - Kim, Sujin

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