A5034300365- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Muscle Physiology and Disorders
- Calcium signaling and nucleotide metabolism
- PI3K/AKT/mTOR signaling in cancer
- Peptidase Inhibition and Analysis
- Osteoarthritis Treatment and Mechanisms
- Photoreceptor and optogenetics research
- Cardiomyopathy and Myosin Studies
- Metabolism, Diabetes, and Cancer
- Genetic and Kidney Cyst Diseases
- Antimicrobial Peptides and Activities
- Wnt/β-catenin signaling in development and cancer
- Heme Oxygenase-1 and Carbon Monoxide
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- Redox biology and oxidative stress
- Prostate Cancer Treatment and Research
- Calpain Protease Function and Regulation
- Protease and Inhibitor Mechanisms
- Folate and B Vitamins Research
- Advanced Fluorescence Microscopy Techniques
- Lysosomal Storage Disorders Research
Monash University
2010-2021
Australian Regenerative Medicine Institute
2019-2021
Peter MacCallum Cancer Centre
2013
Institut de génétique et de biologie moléculaire et cellulaire
2013
Inositol polyphosphate 4-phosphatase-II (INPP4B) is a regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway and implicated as tumor suppressor in epithelial carcinomas. INPP4B loss heterozygosity (LOH) detected some human breast cancers; however, expression protein cancer subtypes normal unknown. We report here that expressed nonproliferative estrogen receptor (ER)-positive cells breast, ER-positive, but not negative, cell lines. knockdown ER-positive increased Akt activation,...
Rab/Ypt GTPases play key roles in the regulation of vesicular trafficking. They perform most their functions a GTP-bound form by interacting with specific downstream effectors. The exocyst is complex eight polypeptides involved constitutive secretion and as an effector for multiple Ras-related small GTPases, including Rab protein Sec4p yeast. In this study, we have examined localization function Sec15 subunit mammalian cells. Overexpressed associated clusters tubular/vesicular elements that...
Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to and is mutated in JBTS. Murine Inpp5e ablation embryonically lethal recapitulates JBTS, neural tube defects polydactyly; however, the underlying signaling function of at are still emerging. We report Inpp5e−/− embryos exhibit aberrant Hedgehog-dependent patterning with reduced Hedgehog signaling. Using mouse genetics, we show increasing via...
The regulation of autophagy-dependent lysosome homeostasis in vivo is unclear. We showed that the inositol polyphosphate 5-phosphatase INPP5K regulates autophagic reformation (ALR), a recycling pathway, muscle. hydrolyzes phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol 4-phosphate [PI(4)P], and mutations cause muscular dystrophy by unknown mechanisms. report loss muscle caused severe disease, autophagy inhibition, depletion. Reduced PI(4,5)P2 turnover on...
Abstract INPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P 2 to PI(3)P and inactivation is common in triple-negative breast cancer. Paradoxically, also a reported oncogene other cancers. How these opposing roles relate PI3K regulation unclear. We report PIK3CA -mutant ER + cancers exhibit increased mRNA protein expression the proliferation tumor growth of cancer cells, despite suppression AKT signaling. used integrated proteomics, transcriptomics imaging demonstrate localized late...
ABSTRACT We report that chloromethyl-X-rosamine (MitoTracker Red), a mitochondrion-selective fluorescent probe, has strong photosensitising action. Photoirradiation of intact cells loaded with induces depolarisation the inner mitochondrial membrane and swelling mitochondria, subsequently resulting in apoptosis. have studied human osteosarcoma 143B TK− (ρ+) derived ρ0 206 cell line devoid DNA. Colony formation tests revealed itself no toxicity to either concentration range 100-250 nM (unless...
Abstract It is now clear that progression from localized prostate cancer to incurable castrate-resistant (CRPC) driven by continued androgen receptor (AR), signaling independently of androgen. Thus, there remains a strong rationale suppress AR activity as the single most important therapeutic goal in CRPC treatment. Although expression ligand-independent splice variants confers resistance AR-targeted therapy and lethal cancer, molecular regulators remain unclear, particular those pathways...
Polycystic kidney disease (PKD) is a common cause of renal failure with few effective treatments. INPP5E an inositol polyphosphate 5-phosphatase that dephosphorylates phosphoinositide 3-kinase (PI3K)-generated PI(3,4,5)P3 and mutated in ciliopathy syndromes. Germline Inpp5e deletion embryonically lethal, attributed to cilia stability defects, associated polycystic kidneys. However, the molecular mechanisms responsible for PKD development upon loss remain unknown. Here, we show conditional...
Members of the SNARE (soluble N -ethylmaleimide-sensitive fusion protein attachment receptor) superfamily [syntaxins, VAMPs (vesicle-associated membrane proteins) and SNAP25 (synaptosome-associated protein-25)-related proteins] are required for intracellular membrane-fusion events in eukaryotes. In neurons, assembly core complexes comprising presynaptic membrane-associated SNAREs syntaxin 1 SNAP25, vesicle-associated VAMP2, is necessary synaptic vesicle exocytosis. Several accessory factors...
1. An enzyme that degrades proteoglycan at neutral pH was extracted with 4 M-guanidine hydrochloride from the articular cartilage of rabbits antigen-induced arthritis. 2. The had an apparent molecular weight on Ultrogel AcA 54 about 8000 and optimally active 7.5 in Tris/HCl buffer containing 0.2 M-NaCl. partially purified preparation totally inhibited by 0.01 mM-N-acetyldialanylprolylvalylchloromethane, severely 2 mM-phenylmethanesulphonyl fluoride soya-bean trypsin inhibitor (200...
Exogenous delivery of carrier-linked phosphatidylinositol 3-phosphate [PtdIns(3)P] to adipocytes promotes the trafficking, but not insertion, glucose transporter GLUT4 into plasma membrane. However, it is yet be demonstrated if endogenous PtdIns(3)P regulates trafficking and, in addition, metabolic pathways mediating membrane synthesis are uncharacterized. In unstimulated 3T3-L1 adipocytes, conditions under which PtdIns(3,4,5)P3 was synthesized, ectopic expression wild-type, catalytically...
Phosphoinositide 3-kinase (PI3K) regulates cell polarity and migration by generating phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) at the leading edge of migrating cells. The serine-threonine protein kinase Akt binds to PI(3,4,5)P3, resulting in its activation. Active promotes spatially regulated actin cytoskeletal remodeling thereby directed migration. inositol polyphosphate 5-phosphatases (5-ptases) degrade PI(3,4,5)P3 form PI(3,4)P2, which leads diminished Several 5-ptases,...
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD complex and the primary pathogenic insult underlying muscle unknown. Several candidate genes have been proposed including DUX4 FRG1. Expression analysis studies report deregulation which mediate myoblast differentiation fusion. Transgenic mice overexpressing FRG1 recapitulate phenotype. Our current study selectively examines how increased expression may...
Rabbit peritoneal polymorphonuclear neutrophils (PMN), incubated in medium containing [35S]sulphate, incorporated 35S into proteoglycan and protein fractions. Approximately 46% of the 35S-labelled macromolecules associated with PMN cells after 1 h incubation were recovered a cytoplasmic granule extract, majority being present azurophil granules. Analysis fraction showed that approximately 90% proteoglycans. When challenged heat-aggregated rabbit gamma-globulin presence cytochalasin B cGMP,...
The incorporation of [35S]sulphate into macromolecules by rabbit peritoneal polymorphonuclear neutrophils (PMN) in vitro revealed that two major groups 35S-labelled were synthesized these cells. first group did not bind to anion-exchange columns at pH 6.0 and contained 60-80% the total incorporated radiolabel. second eluted as a single peak radioactivity an ionic strength characteristic sulphated proteoglycans; it accounted for remaining Analysis this material on Sepharose CL-6B demonstrated...
The mechanism of transport alanine and aminoisobutyric acid into chondrocytes in rabbit articular cartilage was shown to be mediated by systems similar that described for other eukaryotic cells namely the A, ASC, L systems. Three days after initiation an acute inflammatory arthritis intra-articular injection carrageenin one knee joint rate both these amino acids decreased. Although all three were depressed, it appeared A ASC partially susceptible damage induced inflammation. affected had...