Claudio A Joazeiro, Ph.D.
Professor
About Claudio A Joazeiro
website: www.joazeirolab.com
Additional Positions:
Associate Professor, Molecular Medicine
2017 – 2018
·
Scripps Research
Associate Professor, Cell and Molecular Biology (CMB)
2013 – 2017
·
Scripps Research
Assistant Professor, Cell Biology
2006 – 2012
·
Scripps Research
Related Links:
Accomplishments
1st Brazilian Diaspora Prize “Professional of the Year” in the Human Health sector
2014
·
Brazil’s Ministry of Development, Industry and Commerce
Cancer Research Scholar
2009-2012
·
2000 American Cancer Society
Career Development Award
2000
·
Leukemia and Lymphoma Society
Research Profile
See lab website: www.joazeirolab.com
Role of the ubiquitin-proteasome system in cellular regulation and disease
E3 ubiquitin ligases are the components that confer specificity to the ubiquitin system. Consistent with their critical role in cellular regulation, mutations affecting E3s can cause human disease—as illustrated by the cases of BRCA1 in breast cancer and of Parkin in Parkinsonism. Our laboratory is engaged in three main areas of research related to E3s:
1] We are interested in elucidating E3s’ function and mechanisms. For this purpose, we utilize cell and molecular biology approaches with mammalian cells, mice and yeast; our expertise is complemented by close collaborations on structural biology, bioinformatics, mass spectrometry, next-generation sequencing, and fly models;
2]We utilize the information we learn from the above studies to develop assays that are amenable to high-throughput screening, which are then used to identify small molecule inhibitors of E3 ligases. Such compounds can then be both turned into tools to interrogate biology, and developed as pharmaceutical drug candidates;
3] We collaborate with clinicians to translate our basic research findings into therapeutically-relevant discoveries.
Open Researcher and Contributor ID (ORCID)
0000-0003-1433-8013
Areas of Interest
- Microbiology
- Molecular therapy
- Neurodegenerative diseases
- Protein biochemistry
- RNA binding proteins
- Rare neuromuscular disorders
- Small molecule drug discovery
Publications
2023
Mechanism and evolutionary origins of alanine-tail C-degron recognition by E3 ligases Pirh2 and CRL2-KLHDC10
Cell Reports.
42(9)
[DOI] 10.1016/j.celrep.2023.113100.
[PMID] 37676773.
2023
Mechanism and evolutionary origins of Alanine-tail C-degron recognition by E3 ligases Pirh2 and CRL2-KLHDC10.
bioRxiv : the preprint server for biology.
[DOI] 10.1101/2023.05.03.539038.
[PMID] 37205381.
2022
Bacterial ribosome collision sensing by a MutS DNA repair ATPase paralogue
Nature.
603(7901):509-514
[DOI] 10.1038/s41586-022-04487-6.
[PMID] 35264791.
2022
Ribosome-associated quality-control mechanisms from bacteria to humans.
Molecular cell.
82(8):1451-1466
[DOI] 10.1016/j.molcel.2022.03.038.
[PMID] 35452614.
2021
Convergence of mammalian RQC and C-end rule proteolytic pathways via alanine tailing.
Molecular cell.
81(10):2112-2122.e7
[DOI] 10.1016/j.molcel.2021.03.004.
[PMID] 33909987.
2021
Mimicry of Canonical Translation Elongation Underlies Alanine Tail Synthesis in RQC.
Molecular cell.
81(1):104-114.e6
[DOI] 10.1016/j.molcel.2020.11.001.
[PMID] 33259811.
2020
Author Correction: NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease.
Nature communications.
11(1)
[DOI] 10.1038/s41467-020-18941-4.
[PMID] 33004807.
2020
Decision letter: Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection
.
[DOI] 10.7554/elife.58277.sa1.
2020
NEMF mutations that impair ribosome-associated quality control are associated with neuromuscular disease.
Nature communications.
11(1)
[DOI] 10.1038/s41467-020-18327-6.
[PMID] 32934225.
2019
Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control.
Cell.
178(1):76-90.e22
[DOI] 10.1016/j.cell.2019.05.002.
[PMID] 31155236.
2019
Mechanisms and functions of ribosome-associated protein quality control.
Nature reviews. Molecular cell biology.
20(6):368-383
[DOI] 10.1038/s41580-019-0118-2.
[PMID] 30940912.
2017
Ribosomal Stalling During Translation: Providing Substrates for Ribosome-Associated Protein Quality Control.
Annual review of cell and developmental biology.
33:343-368
[DOI] 10.1146/annurev-cellbio-111315-125249.
[PMID] 28715909.
2016
Author response: The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation
.
[DOI] 10.7554/elife.11794.015.
2016
Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits.
Proceedings of the National Academy of Sciences of the United States of America.
113(29):E4151-60
[DOI] 10.1073/pnas.1605951113.
[PMID] 27385828.
2016
The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation
eLife.
5
[DOI] 10.7554/elife.11794.
2014
Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity.
FEBS letters.
588(23):4422-30
[DOI] 10.1016/j.febslet.2014.10.013.
[PMID] 25448680.
2014
Structural basis for translational surveillance by the large ribosomal subunit-associated protein quality control complex.
Proceedings of the National Academy of Sciences of the United States of America.
111(45):15981-6
[DOI] 10.1073/pnas.1413882111.
[PMID] 25349383.
2014
Ubiquitylation by the Ltn1 E3 ligase protects 60S ribosomes from starvation-induced selective autophagy.
The Journal of cell biology.
204(6):909-17
[DOI] 10.1083/jcb.201308139.
[PMID] 24616224.
2013
Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase.
Proceedings of the National Academy of Sciences of the United States of America.
110(5):1702-7
[DOI] 10.1073/pnas.1210041110.
[PMID] 23319619.
2011
Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients.
Human molecular genetics.
20(18):3642-52
[DOI] 10.1093/hmg/ddr284.
[PMID] 21685205.
2010
Role of a ribosome-associated E3 ubiquitin ligase in protein quality control.
Nature.
467(7314):470-3
[DOI] 10.1038/nature09371.
[PMID] 20835226.
2009
A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration.
Proceedings of the National Academy of Sciences of the United States of America.
106(7):2097-103
[DOI] 10.1073/pnas.0812819106.
[PMID] 19196968.
2009
RING domain E3 ubiquitin ligases.
Annual review of biochemistry.
78:399-434
[DOI] 10.1146/annurev.biochem.78.101807.093809.
[PMID] 19489725.
2008
Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling.
PloS one.
3(1)
[DOI] 10.1371/journal.pone.0001487.
[PMID] 18213395.
2006
Discovery of EGFR selective 4,6-disubstituted pyrimidines from a combinatorial kinase-directed heterocycle library.
Journal of the American Chemical Society.
128(7):2182-3
[PMID] 16478150.
2006
Proteasome inhibitor drugs on the rise.
Cancer research.
66(16):7840-2
[PMID] 16861477.
2006
The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes.
Genes & development.
20(5):586-600
[PMID] 16510874.
2005
Methods for the functional genomic analysis of ubiquitin ligases.
Methods in enzymology.
398:280-91
[PMID] 16275336.
2005
Ubiquitin ligase activity of TFIIH and the transcriptional response to DNA damage.
Molecular cell.
18(2):237-43
[PMID] 15837426.
2003
Conformational flexibility underlies ubiquitin ligation mediated by the WWP1 HECT domain E3 ligase.
Molecular cell.
11(1):249-59
[PMID] 12535537.
2003
Ubiquitin signals protein trafficking via interaction with a novel ubiquitin binding domain in the membrane fusion regulator, Vps9p.
Current biology : CB.
13(3):258-62
[PMID] 12573224.
2003
Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates.
Proceedings of the National Academy of Sciences of the United States of America.
100(15):8892-7
[PMID] 12857950.
2002
Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation.
Nature immunology.
3(3):281-7
[PMID] 11828324.
2002
The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2.
Molecular cell.
9(5):945-56
[PMID] 12049732.
2001
Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity.
Proceedings of the National Academy of Sciences of the United States of America.
98(9):5134-9
[PMID] 11320250.
2001
E3 ubiquitin-protein ligase activity of Parkin is dependent on cooperative interaction of RING finger (TRIAD) elements.
Journal of biomedical science.
8(5):421-9
[PMID] 11549885.
2001
Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation.
Nature cell biology.
3(1):24-9
[PMID] 11146622.
2000
Biochemistry. Ubiquitination–more than two to tango.
Science (New York, N.Y.).
289(5487):2061-2
[PMID] 11032556.
2000
Brassinosteroid-insensitive-1 is a ubiquitously expressed leucine-rich repeat receptor serine/threonine kinase.
Plant physiology.
123(4):1247-56
[PMID] 10938344.
2000
Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase.
The Journal of biological chemistry.
275(46):35734-7
[PMID] 10940313.
2000
RING finger proteins: mediators of ubiquitin ligase activity.
Cell.
102(5):549-52
[PMID] 11007473.
2000
The APC11 RING-H2 finger mediates E2-dependent ubiquitination.
Molecular biology of the cell.
11(7):2315-25
[PMID] 10888670.
2000
The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7.
The Journal of biological chemistry.
275(35):26661-4
[PMID] 10862606.
1999
The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase.
Science (New York, N.Y.).
286(5438):309-12
[PMID] 10514377.
1996
Alternative outcomes in assembly of promoter complexes: the roles of TBP and a flexible linker in placing TFIIIB on tRNA genes.
Genes & development.
10(6):725-39
[PMID] 8598299.
1995
Yeast RNA polymerase III: transcription complexes and RNA synthesis.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.
28(2):147-59
[PMID] 7581036.
1994
Identical components of yeast transcription factor IIIB are required and sufficient for transcription of TATA box-containing and TATA-less genes.
Molecular and cellular biology.
14(4):2798-808
[PMID] 8139577.
1992
The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor, TFIIIB.
Cell.
71(6):1055-64
[PMID] 1458536.
1991
Isolation of Drosophila genes encoding G protein-coupled receptor kinases.
Proceedings of the National Academy of Sciences of the United States of America.
88(24):11067-70
[PMID] 1662381.
1990
Generation of cell lines to study the role played by oncogenes and anti-oncogenes in cell proliferation control.
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.
23(9):795-9
[PMID] 2101319.
1988
Generation of myc/fos transfectant Balb-3T3 cell lines.
Archivos de biologia y medicina experimentales.
21(3-4):429-33
[PMID] 3256275.
Grants
Jun 2022
ACTIVE
POLYALANINE TAILS: A NOVEL TYPE OF PROTEIN MODIFICATION IMPLICATED IN NEURODEGENERATION
Role: Principal Investigator
Funding: THE JACKSON LABORATORY
via NATL INST OF HLTH NINDS
Education
Ph.D.
1996
·
University of California, San Diego
Master's of Science
1990
·
University of Sao Paulo
Contact Details
Phones:
- Business:
- (561) 228-3211
Emails:
- Business:
- cjoazeiro@ufl.edu
Addresses:
- Business Mailing:
-
C249
130 SCRIPPS WAY BLDG 2C2
Jupiter FL 33458