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PROM1-mediated cell signal transduction in cancer stem cells and hepatocytes
Myeong-Suk Bahn,고영규 생화학분자생물학회 2023 BMB Reports Vol.56 No.2
Prominin-1 (PROM1), also called CD133, is a penta-span transmembraneprotein that is localized in membrane protrusions,such as microvilli and filopodia. It is known to be expressed incancer stem cells and various progenitor cells of bone marrow,liver, kidney, and intestine. Accumulating evidence has revealedthat PROM1 has multiple functions in various organs, such aseye, tooth, peripheral nerve, and liver, associating with variousmolecular protein partners. PROM1 regulates PKA-induced gluconeogenesis,TGFβ-induced fibrosis, and IL-6-induced regenerationin the liver, associating with Radixin, SMAD7, and GP130,respectively. In addition, PROM1 is necessary to maintain cancerstem cell properties by activating PI3K and β-Catenin. PROM1-deficienct mice also show distinct phenotypes in eyes, brain,peripheral nerves, and tooth. Here, we discuss recent findingsof PROM1-mediated signal transduction.
Hepatocyte-specific Prominin-1 protects against liver injury-induced fibrosis by stabilizing SMAD7
Lee Hyun,Yu Dong-Min,Bahn Myeong-Suk,Kwon Young-Jae,Um Min Jee,Yoon Seo Yeon,Kim Ki-Tae,Lee Myoung-Woo,Jo Sung-Je,Lee Sungsoo,Koo Seung-Hoi,Jung Ki Hoon,Lee Jae-Seon,Ko Young-Gyu 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (Prom1CreER; R26TdTom) in which cells expressed TdTom under control of the Prom1 promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific Prom1-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific Prom1 deficiency but not by cholangiocyte-specific Prom1 deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific Prom1-deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFβ signaling during liver fibrosis.
Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction
Yu, Dong‐,Min,Jung, Seung Hee,An, Hyoung‐,Tae,Lee, Sungsoo,Hong, Jin,Park, Jun Sub,Lee, Hyun,Lee, Hwayeon,Bahn, Myeong‐,Suk,Lee, Hyung Chul,Han, Na‐,Kyung,Ko, Jesang,Lee, Jae BLACKWELL PUBLISHING 2017 AGING CELL Vol.16 No.4
<P><B>Summary</B></P><P>Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1<SUP><I>−/−</I></SUP> mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD<SUP>+</SUP>/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.</P>