A5074262018- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Atherosclerosis and Cardiovascular Diseases
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- Viral Infectious Diseases and Gene Expression in Insects
- Renal and related cancers
- 14-3-3 protein interactions
- Retinoids in leukemia and cellular processes
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- Pluripotent Stem Cells Research
- Hedgehog Signaling Pathway Studies
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- Multiple Myeloma Research and Treatments
The University of Texas Health Science Center at San Antonio
2004-2021
The University of Texas Health Science Center at Houston
2021
University of Hyderabad
2010
George Washington University
2010
Washington University Medical Center
2010
Harvard University
1995-1997
University of California, Los Angeles
1989-1994
The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and vitro, was found to be degraded by the ubiquitin-proteasome pathway. human ubiquitin-conjugating enzymes Ubc2 Ubc3 were specifically involved ubiquitination p27. Compared with proliferating cells, quiescent cells exhibited a smaller amount ubiquitinating activity, which accounted for marked increase half-life measured these cells. Thus, abundance regulated degradation. specific proteolysis may...
Many DNA tumor viruses express a protein that inhibits transcriptional activation by the tumor-suppressing transcription factor p53. We report adenovirus E1B 55K represses p53-mediated mechanism not described previously. binds p53 without displacing it from its DNA-binding site. A fusion of to GAL4 domain variety promoters with engineered upstream GAL4-binding sites. Mutations within interfere transforming activity and ability inhibit trans-activation also repression GAL4-55K fusion. These...
BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced protein is associated with sporadic cancer cases in these tissues. At the cellular level, plays critical role multiple functions such as DNA repair cell cycle checkpoint control. Its level regulated cycle-dependent manner. However, regulation stability not fully understood. Our earlier study showed that amino terminus harbors degron sequence sufficient necessary conferring...
The cell division cycle gene, CDC34 , is required for ubiquitin-mediated degradation of G 1 regulators and progression through the transition from to S phase in budding yeast. A requirement onset higher eukaryotes has not been established. Studies simple embryonic Xenopus laevis eggs demonstrated that Cdc34p a large molecular size complex was initiation DNA replication. appears regulate function Cdk2–cyclin E, perhaps cdk inhibitor, Xic1.
Abstract Estrogen receptor (ER) signaling plays an important role in breast cancer progression, and ER functions are influenced by coregulatory proteins. PELP1 (proline-, glutamic acid–, leucine-rich protein 1) is a nuclear coregulator that signaling. Its expression deregulated hormonal cancers. We identified as novel cyclin-dependent kinase (CDK) substrate. Using site-directed mutagenesis vitro assays, we Ser477 Ser991 of CDK phosphorylation sites. the phospho-specific antibody, show...
During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it ubiquitinated degraded. In this study, we show that predominant E3 for in egg Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4(Cdt2)) ubiquitin ligase. The addition of full-length XCdt2 extract promotes turnover, while N-terminal domain (residues 1 400) cannot promote despite its ability bind...
Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during cancer development progression less clear. Here, we show that GLI3, a key SHH effector, transcriptionally upregulated androgen deprivation posttranslationally stabilized cells by mutation speckle-type POZ protein (SPOP). GLI3 substrate SPOP-mediated proteasomal degradation driver mutations SPOP...
The ubiquitin-conjugating enzyme, CDC34, has been implicated in the ubiquitination of a number vertebrate substrates, including p27Kip1, IκBα, Wee1, and MyoD. We show that mammalian CDC34 is phosphoprotein phosphorylated proliferating cells. By yeast two-hybrid screening, we identified regulatory (β) subunit human casein kinase 2 (CK2) as CDC34-interacting protein interacts vivo with CK2β transfected specifically vitro by recombinant CK2 HeLa nuclear extract at five sites within...
The regulation of the vertebrate cell cycle is controlled by function cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors. Xenopus laevis kinase inhibitor, p27Xic1 (Xic1) a member p21Cip1/p27Kip1/p57Kip2 inhibitor family inhibits CDK2-cyclin E in vitro as well DNA replication egg extracts. Xic1 targeted for degradation interphase extracts manner dependent on both ubiquitin conjugating enzyme, Cdc34, nuclei. Here we show that ubiquitination occurs exclusively nucleus nuclear...
The Xenopus cyclin-dependent kinase (CDK) inhibitor, p27Xic1 (Xic1), binds to CDK2-cyclins and proliferating cell nuclear antigen (PCNA), inhibits DNA synthesis in extracts, is targeted for ubiquitin-mediated proteolysis. Previous studies suggest that Xic1 ubiquitination degradation are coupled the initiation of replication, but precise timing molecular mechanism proteolysis has not been determined. Here we demonstrate temporally restricted late replication following requirements polymerase...
Abstract Background The SCF skp2 complex is an E3 ubiquitin ligase that known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation division has been well documented, additional functions differentiation, the nervous system, have not investigated. Results Using Xenopus as model here we demonstrate differentiation primary neurons, first neurons differentiate neural plate. shows dynamic expression pattern early...
Human Cdc34 is an ubiquitin conjugating enzyme or E2 that ubiquitinates substrates including p27(Kip1), IkappaBalpha, Wee1, and MyoD. possesses a core catalytic domain encoding the active site cysteine acidic tail within carboxyl terminal 36 amino acids. Studies suggest phosphorylated in mammalian cells at 5 potential residues domain. In order to study biological significance of possible phosphorylation this region, we tested ability human mutants complement cdc34-2 temperature sensitive...
Cell cycle progression is regulated by cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors. In the frog, Xenopus laevis, inhibitor p27Xic1 (Xic1) inhibits DNA synthesis negatively regulating CDK2-cyclin E. Using frog egg extract as a model system for study of Xic1, studies have demonstrated that Xic1 protein levels are nuclear ubiquitination proteolysis. To characterize molecular mechanism regulates turnover, we identified minimal sequences necessary sufficient its degradation....
In the frog, Xenopus laevis, Cip/Kip-type cyclin-dependent kinase (CDK) inhibitor, Xic1, inhibits DNA replication in interphase egg extracts through binding of CDK2-cyclins and Proliferating Cell Nuclear Antigen (PCNA). During polymerase switching replicating extract, Xic1 is targeted for ubiquitination degradation when localized to chromatin its PCNA. To date, machinery responsible unknown although it predicted that E3 called SCF may mediate ubiquitination, characterization lacking. this...
The RNA polymerase II transcriptional Mediator subunit Med12 is broadly implicated in vertebrate brain development, and genetic variation human MED12 associated with X-linked intellectual disability neuropsychiatric disorders. Although prior studies have begun to elaborate the functional contribution of within key neurodevelopmental pathways, a more complete description function developing nervous system, including specific biological networks cellular processes under its regulatory...
Cell division is positively regulated by cyclin-dependent kinases (CDKs) partnered with cyclins and negatively CDK inhibitors. In the frog, Xenopus laevis, three types of inhibitors have been described: p27Xic1 (Xic1) which shares sequence homology both p21Cip1 p27Kip1 from mammals, p16Xic2 (Xic2) p21Cip1, p17Xic3 (Xic3) p27Kip1. While past studies demonstrated that during DNA polymerase switching, Xic1 targeted for protein turnover dependent upon DNA, Proliferating Nuclear Antigen (PCNA),...