A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis

Wang, Y.; Guan, Xin; Fok, Kin Lam; Li, S.; Zhang, X.; Miao, Shiying; Zong, Shudong; Koide, S. S.; Chan, H. P.; Wang, L.

doi:10.1007/s00018-008-8452-0

Cited by 47 publications

(53 citation statements)

References 26 publications

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“…We have previously demonstrated that the heavy subunit of the Gal/GalNAc lectin is a target for EhROM1, but additional targets could also be present. Rhomboid proteases have been implicated in development, signaling, apoptosis, and host cell entry (3,11,49,53,58,60). Thus, roles in adhesion and phagocytosis would both be new functions for rhomboid proteases.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of an Entamoeba histolytica Rhomboid Protease Reveals Roles in Regulating Parasite Adhesion and Phagocytosis

et al. 2010

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Entamoeba histolytica is a deep-branching eukaryotic pathogen. Rhomboid proteases are intramembrane serine proteases, which cleave transmembrane proteins in, or in close proximity to, their transmembrane domain. We have previously shown that E. histolytica contains a single functional rhomboid protease (EhROM1) and has unique substrate specificity. EhROM1 is present on the trophozoite surface and relocalizes to internal vesicles during erythrophagocytosis and to the base of the cap during surface receptor capping. In order to further examine the biological function of EhROM1 we downregulated EhROM1 expression by >95% by utilizing the epigenetic silencing mechanism of the G3 parasite strain. Despite the observation that EhROM1 relocalized to the cap during surface receptor capping, EhROM1 knockdown [ROM(KD)] parasites had no gross changes in cap formation or complement resistance. However, ROM(KD) parasites demonstrated decreased host cell adhesion, a result recapitulated by treatment of wild-type parasites with DCI, a serine protease inhibitor with activity against rhomboid proteases. The reduced adhesion phenotype of ROM(KD) parasites was noted exclusively with healthy cells, and not with apoptotic cells. Additionally, ROM(KD) parasites had decreased phagocytic ability with reduced ingestion of healthy cells, apoptotic cells, and rice starch. Decreased phagocytic ability is thus independent of the reduced adhesion phenotype, since phagocytosis of apoptotic cells was reduced despite normal adhesion levels. The defect in host cell adhesion was not explained by altered expression or localization of the heavy subunit of the Gal/GalNAc surface lectin. These results suggest no significant role of EhROM1 in complement resistance but unexpected roles in parasite adhesion and phagocytosis.

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Section: Discussionmentioning

confidence: 99%

Downregulation of an Entamoeba histolytica Rhomboid Protease Reveals Roles in Regulating Parasite Adhesion and Phagocytosis

et al. 2010

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“…Among the members of the family Rhomboid proteases are found to be responsible for regulating cell growth and development via EGF receptor signaling pathways (7,8). The Rhomboid genes are classified into three groups in vertebrates as, active cellular rhomboids, inactive cellular rhomboids and mitochondrial rhomboids (9,10). Among these, Rhomboid domain containing 1 (RHBDD1) gene is classified under the first category and responsible for releasing mammalian rhomboid protease.…”

Section: Introductionmentioning

confidence: 99%

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Wei

Chen

et al. 2014

Technol Cancer Res Treat

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Abbreviation: RHBDD1: Rhomboid Domain Containing 1; shRNA: Short Hairpin RNAs; RNAi: RNA Interference.Rhomboid domain containing 1 (RHBDD1) gene, a new member of rhomboid family of proteins is highly responsible for the regulation of apoptosis by cleaving pro-apoptotic Bcl-2 family protein BIK. Therefore, the higher expression levels of RHBDD1 in cancer tissues may have a direct influence on cancer progression by arresting apoptosis. With this background this study was focused to find out the effect of RHBDD1 silencing on the progression of human brain glioblastoma cells, U251 and U87MG. The results indicated that both cell lines show a higher expression level of RHBDD1 and RNA interference (RNA) mediated gene silencing successfully down regulated the RHBDD1 gene expression. As a result of RHBDD1 silencing the proliferation of both cell types was reduced by over 50%, 5 days after silencing. Moreover the colony formation was completely inhibited and there were no cells present following two week RHBDD1 gene silencing. The cell proliferation was inhibited as a result of cell cycle arrest due to RHBDD1 absence. Therefore, these results clearly indicate that, RHBDD1 is essential for the progression of glioblastoma cells and silencing of it is resulting in significant inhibition of cell cycle progression and cell proliferation. Collectively, this study shows that RHBDD1 gene engineering could be used as an effective tool in malignant brain tumor therapy.

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“…The HZF1 gene [130] plays an important role in erythroid and megakaryocytic differentiation. RHBDD1 [131] encodes a protein that can act as a serine protease that participates in the cleavage of BIK, a proapoptotic member of the Bcl-2 family, and modulates BIK-mediated apoptotic activity. The gene MAN2C1 obtained from the human tonsil cell cDNA library encodes an important cellular alpha-mannosidase [132].…”

Section: Svh Has Four Splicing Variants Svh-a Svh-b Svh-c and Svh-d;mentioning

confidence: 99%

Literature and patent analysis of the cloning and identification of human functional genes in China

Xia

Tang

Yao

et al. 2012

Sci. China Life Sci.

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A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis

Cited by 47 publications

References 26 publications

Downregulation of an Entamoeba histolytica Rhomboid Protease Reveals Roles in Regulating Parasite Adhesion and Phagocytosis

Downregulation of an Entamoeba histolytica Rhomboid Protease Reveals Roles in Regulating Parasite Adhesion and Phagocytosis

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Literature and patent analysis of the cloning and identification of human functional genes in China

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