- Renal and related cancers
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Biomedical Text Mining and Ontologies
- Cell Image Analysis Techniques
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Tuberous Sclerosis Complex Research
- Cancer Genomics and Diagnostics
- Drug Transport and Resistance Mechanisms
- Cell death mechanisms and regulation
- Metabolism, Diabetes, and Cancer
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Nitric Oxide and Endothelin Effects
- Mast cells and histamine
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Pharmacological Effects and Toxicity Studies
- Cystic Fibrosis Research Advances
- Renin-Angiotensin System Studies
- Cancer Research and Treatments
University of Concepción
2016-2025
US Biologic (United States)
2011
UCSF Helen Diller Family Comprehensive Cancer Center
2008-2010
University of California, San Francisco
1972-2010
Indiana University School of Medicine
1999-2005
Indiana University – Purdue University Indianapolis
1999-2005
University Hospital and Clinics
2002
University Medical Center
2002
The University of Texas Medical Branch at Galveston
1997-1999
University of Buenos Aires
1997-1998
Recently the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product has been identified as a negative regulator of protein synthesis upstream mTOR and ribosomal S6 kinases. Because homology TSC2 with GTPase-activating proteins for Rap1, we examined whether Ras/Rap-related GTPase might be involved in this process. was found to bind Rheb-GTP vitro reduce Rheb GTP levels vivo. Over-expression but not Rap1 promoted activation kinase rapamycin-dependent manner, suggesting that acts...
Epac-1 and -2 (exchange proteins directly activated by cyclic AMP) are guanine-nucleotide exchange factors for the GTPases Rap1 -2. Epac2 but not Epac1 was found to possess a RA (Ras association) domain similar that in Ras effector Ral-GDS. This specifically bound Ras-GTP, enabling oncogenic translocate from cytosol plasma membrane. Consequently, small pool of membrane-bound at expense bulk located on intracellular organelles. Whereas translocation mimicked challenge with epidermal growth...
Abstract Protein kinase CK2 is a highly conserved and constitutively active Ser/Thr-kinase that phosphorylates large number of substrates, resulting in increased cell proliferation survival. A known target Akt, player the PI3K/Akt/mTORC1 signaling pathway, which aberrantly activated 32% colorectal cancer (CRC) patients. On other hand, mTORC1 plays an important role regulation protein synthesis, growth, autophagy. Some studies suggest regulates several cancers. The most recently developed...
M-Ras is a Ras-related protein that shares approximately 55% identity with K-Ras and TC21. The message was widely expressed but most predominant in ovary brain. Similarly to Ha-Ras, expression of mutationally activated NIH 3T3 mouse fibroblasts or C2 myoblasts resulted cellular transformation inhibition differentiation, respectively. only weakly extracellular signal-regulated kinase 2 (ERK2), it cooperated Raf, Rac, Rho induce transforming foci cells, suggesting signaled via alternate...
Abstract The type 1 TNFR (TNFR1) contains a death domain through which it interacts with other death-domain proteins to promote cellular responses. However, signaling does not explain how TNFR1 induces the tyrosine phosphorylation of intracellular proteins, are important responses induced by TNFR1. In this study, we show that associates Jak2, c-Src, and PI3K in various cell types. Jak2 c-Src constitutively associate active complex. Stimulation TNF time-dependent change level associated...
Abstract Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In four paralogues have been identified (SALL1-4), and SALL2 is the family’s most dissimilar member. required during brain eye It downregulated cancer acts as a tumor suppressor, promoting cell cycle arrest death. Despite its functions, information about regulation scarce. Public data indicate that ubiquitinated phosphorylated several residues...
Many membrane proteins that belong to the ATP-binding cassette (ABC) superfamily are clinically important, including cystic fibrosis transmembrane conductance regulator, sulphonylurea receptor and P-glycoprotein (multidrug resistance gene product; MDR1). These contain two multispanning domains, each followed by one nucleotide-binding domain (NBD) a linker region distal first NBD. ATP hydrolysis NBDs is critical for ABC protein function; seems have regulatory role. Previous attempts express...
Abstract AND-34, a 95-kDa protein with modest homology to Ras GDP exchange factors, associates the focal adhesion p130Cas. Overexpression of AND-34 confers anti-estrogen resistance in breast cancer cell lines, property linked its ability activate Rac. Here, we show that both factor–like domain and SH2 are required for Rac activation estrogen receptor (ER) antagonist ICI 182,780. As phosphatidylinositol 3-kinase (PI3K) signaling can regulate activation, examined effects on PI3K. MCF-7 cells...
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family factors involved in development and conserved through evolution. Since its identification 1996, findings indicate that SALL2 plays role neurogenesis, neuronal differentiation eye development. Consistently, deficiency associates with neural tube defects coloboma, congenital disease. Relevant to cancer, clinical studies deregulated various cancers specific biomarker for Synovial Sarcoma. However,...
NUAK1 is an AMPK-related kinase located in the cytosol and nucleus, whose expression associates with tumor malignancy poor patient prognosis several cancers. Accordingly, was associated metastasis because it promotes cell migration invasion different cancer cells. Besides, supports survival under metabolic stress maintains ATP levels hepatocarcinoma cells, suggesting a role energy metabolism cancer. However, underlying mechanism for this function, as well its link to subcellular...
We previously found that the small GTPase Rheb regulates cell‐cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1‐independent mechanism. However, biological function of Rheb/p27 axis remains unknown. Here, we show siRNA‐mediated depletion decreases survival human under serum deprivation. As autophagy can support cell survival, analyzed effect on this process detecting modification marker protein LC3 western blot and imunofluorescence. promotes several lines Accordingly, blocking...
Several proteins belonging to the ATP-binding cassette superfamily can affect ion channel function. These include cystic fibrosis transmembrane conductance regulator, sulfonylurea receptor, and multidrug resistance protein P-glycoprotein (MDR1). We measured whole cell swelling-activated Cl − currents ( I Cl,swell ) in parental cells expressing wild-type MDR1 or a phosphorylation-defective mutant (Ser-661, Ser-667, Ser-671 replaced by Ala). Stimulation of kinase C (PKC) with phorbol ester...
SALL2 is a poorly characterized transcription factor that belongs to the Spalt‐like family involved in development. Mutations on have been associated with ocular coloboma and cancer. In cancers, deregulated proposed as tumor suppressor ovarian has implicated stemness, cell death, proliferation, quiescence. However, mechanisms underlying roles of related cancer remain largely unknown. Here, we investigated role proliferation using mouse embryo fibroblasts (MEFs) derived from Sall2 −/− mice....
NUAK1 is a serine/threonine kinase member of the AMPK-α family. regulates several processes in tumorigenesis; however, its regulation and molecular targets are still poorly understood. Bioinformatics analysis predicted that majority localizes nucleus. However, there no studies about subcellular distribution. Here, we analyzed localization human cell lines, mouse embryo fibroblasts, normal tissues. We found located nucleus also cytoplasm. Through bioinformatics comparing wild type mutants,...
Constitutive activation of M-Ras has previously been reported to cause morphologic and growth transformation murine cells, suggesting that plays a role in tumorigenesis. Cell by correlated with weak the Raf/MEK/ERK pathway, although contributions from other downstream effectors were suggested. Recent studies indicate signaling events distinct cascade are critical for human However, it is unknown what triggers cells. Using constitutively active (Q71L) containing additional mutations within...