Critical role for BIM in T cell receptor restimulation-induced death (2008)
Snow, Andrew L, Oliveira, João B, Zheng, Lixin, Dale, Janet K, Fleisher, Thomas A, Lenardo, Michael J
Abstract Background Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR)-triggered propriocidal cell death important for governing the intensity of immune...
14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr (2008)
Bolton, Diane L, Barnitz, Robert A, Sakai, Keiko, Lenardo, Michael J
Abstract Background Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4+ T cell depletion in HIV-1-infected individuals remains unclear. The HIV-1 Vpr...
The control of CD4+CD25+Foxp3+regulatory T cell survival (2008)
Pandiyan, Pushpa, Lenardo, Michael J
Abstract CD4 + CD25 + Foxp3 + regulatory T (T reg ) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in...
Cerutti, Elisa, Campagnoli, Maria F, Ferretti, Massimo, Garelli, Emanuela, Crescenzio, Nicoletta, Rosolen, Angelo, ...
Abstract Background Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood...
Bi, Lilia L, Pan, George, Atkinson, T Prescott, Zheng, Lixin, Dale, Janet K, Makris, Christopher, ...
Abstract Background: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1; TNFRSF6 ),...
Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk (2001)
Chamorro, Mario, Czar, Michael J, Debnath, Jayanta, Cheng, Genhong, Lenardo, Michael J, Varmus, Harold E, ...
Abstract Background The Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this...
HIV-1 Directly Kills CD4+ T Cells by a Fas-independent Mechanism (1998)
Gandhi, Rajesh T., Chen, Benjamin K., Straus, Stephen E., Dale, Janet K., Lenardo, Michael J., Baltimore, David
The mechanism by which HIV-1 induces CD4+ T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected...
Lenardo, Michael J., Kuang, Anna, Gifford, Ann, Baltimore, David
The activity of the enhancer for the κ immunoglobulin light chain gene critically depends on the presence in the nucleus of the NF-κB protein. We purified NF-κB over 50,000-fold and identified two...
Martin, David A., Zheng, Lixin, Siegel, Richard M., Huang, Baohua, Fisher, Galen H., Wang, Jin, ...
Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism....
Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk
Chamorro, Mario, Czar, Michael J, Debnath, Jayanta, Cheng, Genhong, Lenardo, Michael J, Varmus, Harold E, ...
Caspase-10 is an initiator caspase in death receptor signaling
Wang, Jin, Chun, Hyung J., Wong, Wilson, Spencer, David M., Lenardo, Michael J.
A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function...
rlk/TXK Encodes Two Forms of a Novel Cysteine String Tyrosine Kinase Activated by Src Family Kinases
Debnath, Jayantha, Chamorro, Mario, Czar, Michael J., Schaeffer, Edward M., Lenardo, Michael J., Varmus, Harold E., ...
Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near...
Lenardo, Michael J., Angleman, Sara B., Bounkeua, Viengngeun, Dimas, Joseph, Duvall, Melody G., Graubard, Moses B., ...
An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4+ T-lymphocyte destruction. We show here that HIV type 1 (HIV-1) exerts a profound...
Bolton, Diane L., Hahn, Beom-Ik, Park, Eugenia A., Lehnhoff, Laura L., Hornung, Felicita, Lenardo, Michael J.
A critical aspect of AIDS pathogenesis that remains unclear is the mechanism by which human immunodeficiency virus type 1 (HIV-1) induces death in CD4+ T lymphocytes. A better understanding of the...
Garvey, Tara L., Bertin, John, Siegel, Richard M., Wang, Guang-hua, Lenardo, Michael J., Cohen, Jeffrey I.
Molluscum contagiosum virus (MCV), a member of the human poxvirus family, encodes the MC159 protein that inhibits Fas-, tumor necrosis factor (TNF)-, and TNF-related apoptosis-inducing ligant...
Interaction of Histone Acetylases and Deacetylases In Vivo
Yamagoe, Satoshi, Kanno, Tomohiko, Kanno, Yuka, Sasaki, Shigakazu, Siegel, Richard M., Lenardo, Michael J., ...
Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell...
Speirs, Christina, Van Nimwegen, Erik, Bolton, Diane, Zavolan, Mihaela, Duvall, Melody, Angleman, Sara, ...
Human immunodeficiency virus (HIV) causes complex metabolic changes in infected CD4+ T cells that lead to cell cycle arrest and cell death by necrosis. To study the viral functions responsible for...
Garvey, Tara L., Bertin, John, Siegel, Richard M., Wang, Guang-hua, Lenardo, Michael J., Cohen, Jeffrey I.
Clancy, Lauren, Mruk, Karen, Archer, Kristina, Woelfel, Melissa, Mongkolsapaya, Juthathip, Screaton, Gavin, ...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not...
Sakai, Keiko, Dimas, Joseph, Lenardo, Michael J.
HIV type I (HIV-1) can cause G2 cell cycle arrest and death of CD4+ T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytopathicity has...
Martin, David A., Zheng, Lixin, Siegel, Richard M., Huang, Baohua, Fisher, Galen H., Wang, Jin, ...
Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism....
Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk
Chamorro, Mario, Czar, Michael J, Debnath, Jayanta, Cheng, Genhong, Lenardo, Michael J, Varmus, Harold E, ...
Caspase-10 is an initiator caspase in death receptor signaling
Wang, Jin, Chun, Hyung J., Wong, Wilson, Spencer, David M., Lenardo, Michael J.
A role for caspase-10, previously implicated in the autoimmune lymphoproliferative syndrome, in death receptor signaling has not been directly shown. Here we show that caspase-10 can function...
rlk/TXK Encodes Two Forms of a Novel Cysteine String Tyrosine Kinase Activated by Src Family Kinases
Debnath, Jayantha, Chamorro, Mario, Czar, Michael J., Schaeffer, Edward M., Lenardo, Michael J., Varmus, Harold E., ...
Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near...
Lenardo, Michael J., Angleman, Sara B., Bounkeua, Viengngeun, Dimas, Joseph, Duvall, Melody G., Graubard, Moses B., ...
An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4+ T-lymphocyte destruction. We show here that HIV type 1 (HIV-1) exerts a profound...
Bolton, Diane L., Hahn, Beom-Ik, Park, Eugenia A., Lehnhoff, Laura L., Hornung, Felicita, Lenardo, Michael J.
A critical aspect of AIDS pathogenesis that remains unclear is the mechanism by which human immunodeficiency virus type 1 (HIV-1) induces death in CD4+ T lymphocytes. A better understanding of the...
Garvey, Tara L., Bertin, John, Siegel, Richard M., Wang, Guang-hua, Lenardo, Michael J., Cohen, Jeffrey I.
Molluscum contagiosum virus (MCV), a member of the human poxvirus family, encodes the MC159 protein that inhibits Fas-, tumor necrosis factor (TNF)-, and TNF-related apoptosis-inducing ligant...
Interaction of Histone Acetylases and Deacetylases In Vivo
Yamagoe, Satoshi, Kanno, Tomohiko, Kanno, Yuka, Sasaki, Shigakazu, Siegel, Richard M., Lenardo, Michael J., ...
Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell...
Speirs, Christina, Van Nimwegen, Erik, Bolton, Diane, Zavolan, Mihaela, Duvall, Melody, Angleman, Sara, ...
Human immunodeficiency virus (HIV) causes complex metabolic changes in infected CD4+ T cells that lead to cell cycle arrest and cell death by necrosis. To study the viral functions responsible for...
Clancy, Lauren, Mruk, Karen, Archer, Kristina, Woelfel, Melissa, Mongkolsapaya, Juthathip, Screaton, Gavin, ...
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytokine with potential therapeutic value against cancers because of its selective cytotoxicity to many transformed, but not...
Garvey, Tara L., Bertin, John, Siegel, Richard M., Wang, Guang-hua, Lenardo, Michael J., Cohen, Jeffrey I.
Sakai, Keiko, Dimas, Joseph, Lenardo, Michael J.
HIV type I (HIV-1) can cause G2 cell cycle arrest and death of CD4+ T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytopathicity has...
Pathological Findings in Human Autoimmune Lymphoproliferative Syndrome
Lim, Megan S., Straus, Stephen E., Dale, Janet K., Fleisher, Thomas A., Stetler-Stevenson, Maryalice, Strober, Warren, ...
The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present...
Bi, Lilia L, Pan, George, Atkinson, T Prescott, Zheng, Lixin, Dale, Janet K, Makris, Christopher, ...
NRAS mutation causes a human autoimmune lymphoproliferative syndrome
Oliveira, João B., Bidère, Nicolas, Niemela, Julie E., Zheng, Lixin, Sakai, Keiko, Nix, Cynthia P., ...
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization, and other signaling networks, and is the most frequent target of...
Bolton, Diane L., Lenardo, Michael J.
The mechanism of CD4+ T-cell depletion in human immunodeficiency virus type 1 (HIV-1)-infected individuals remains unknown, although mounting evidence suggests that direct viral cytopathicity...
Cerutti, Elisa, Campagnoli, Maria F, Ferretti, Massimo, Garelli, Emanuela, Crescenzio, Nicoletta, Rosolen, Angelo, ...
Siegel, Richard M., Muppidi, Jagan R., Sarker, Malabika, Lobito, Adrian, Jen, Melinda, Martin, David, ...
Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although...
The control of CD4+CD25+Foxp3+ regulatory T cell survival
Pandiyan, Pushpa, Lenardo, Michael J
CD4+CD25+Foxp3+ regulatory T (Treg) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in the periphery is...
Identification of a Novel Developmental Stage Marking Lineage Commitment of Progenitor Thymocytes
Carlyle, James R., Michie, Alison M., Furlonger, Caren, Nakano, Toru, Lenardo, Michael J., Paige, Christopher J., ...
Bipotent progenitors for T and natural killer (NK) lymphocytes are thought to exist among early precursor thymocytes. The identification and functional properties of such a progenitor population...
Wang, Jin, Lenardo, Michael J.
B cells are susceptible to Fas ligand (FasL)+ CD4+ Th1 cell–mediated apoptosis. We demonstrate that blocking the interactions between lymphocyte function associated (LFA)-1 and intercellular...
Selective Induction of Apoptosis in Mature T Lymphocytes by Variant T Cell Receptor Ligands
Combadière, Behazine, E Sousa, Caetano Reis, Germain, Ronald N., Lenardo, Michael J.
Activation, anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or...
HIV-1 Directly Kills CD4+ T Cells by a Fas-independent Mechanism
Gandhi, Rajesh T., Chen, Benjamin K., Straus, Stephen E., Dale, Janet K., Lenardo, Michael J., Baltimore, David
The mechanism by which HIV-1 induces CD4+ T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected...
Death-effector Filaments: Novel Cytoplasmic Structures that Recruit Caspases and Trigger Apoptosis
Siegel, Richard M., Martin, David A., Zheng, Lixin, Ng, Samuel Y., Bertin, John, Cohen, Jeffrey, ...
The death-effector domain (DED) is a critical protein interaction domain that recruits caspases into complexes with members of the TNF-receptor superfamily. Apoptosis can also be induced by...
14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
Bolton, Diane L, Barnitz, Robert A, Sakai, Keiko, Lenardo, Michael J
Critical role for BIM in T cell receptor restimulation-induced death
Snow, Andrew L, Oliveira, João B, Zheng, Lixin, Dale, Janet K, Fleisher, Thomas A, Lenardo, Michael J
Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis
Chun, Hyung J., Ali, Ziad A., Kojima, Yoko, Kundu, Ramendra K., Sheikh, Ahmad Y., Agrawal, Rani, ...
Apelin and its cognate G protein–coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function and a vasodepressor function in the systemic circulation....