BACKGROUND Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been widely used in the treatment of breast cancer through its anti-estrogen activity. Recent studies show that TAM is cytotoxic to both estrogen receptor (ER)-positive and ER-negative cells via the induction of apoptosis. However, the molecular mechanisms of this effect are not well understood. In the present study, we investig...

Protein tyrosine kinases (PTKs) coordinate a broad spectrum of cellular responses to extracellular stimuli and cell-cell interactions during development, tissue homeostasis, and responses to environmental challenges. Thus, an understanding of the regulatory mechanisms that ensure physiological PTK function and potential aberrations of these regulatory processes during diseases such as cancer ar...

Atmospheric convective boundary layer (CBL) entrainment is the downward mixing of free atmospheric air into the CBL as the CBL grows. Primarily, the CBL entrainment is driven by the buoyancy production of turbulence kinetic energy (TKE) due to heating of the lower surface or cooling at the CBL top. The effects of shear-generated turbulence in the CBL are secondary. However, cases of a purely bu...

Cbl is a cytosolic protein that is rapidly tyrosine phosphorylated in response to Fc receptor activation and binds to the adaptor proteins Grb2, CrkL, and Nck. A few reports describe Cbl interactions in primary human hematopoietic cells. We show evidence that Cbl participates in signaling initiated by FcgRI receptor cross-linking in human primary macrophages, and functions downstream of Src fam...

We studied the changes in the proteome of CSF (cerebrospinal fluid) in two animal models of Cbl (cobalamin) deficiency: TGX (totally gastrectomized) rats and rats fed a Cbl-D (Cbl-deficient) diet. Two-dimensional PAGE was used to detect qualitative and quantitative variations in proteins in the CSF samples. The peak increase in total CSF protein concentration was observed 4 months after TG (tot...

c-Cbl, a RING-type ubiquitin E3 ligase, downregulates various receptor tyrosine kinases (e.g., epidermal growth factor receptor (EGFR)), leading to inhibition of cell proliferation. Moreover, patients with myeloid neoplasm frequently harbor c-Cbl mutations, implicating the role of c-Cbl as a tumor suppressor. Recently, we have shown that c-Cbl downregulates αPix-mediated cell migration and inva...

The present study reported that the ubiquitin ligase Cbl-b was up-regulated during anthracycline-induced apoptosis in two cell lines, RBL-2H3 leukemia cells and MGC803 gastric cancer cells. Overexpression of Cbl-b strongly promoted the cytotoxic and apoptosis-inducing effects of anthracyclines, while a dominant negative (DN) Cbl-b mutation abolished these effects in both cell lines. Further inv...

Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support o...

We employed a patterned current blocking layer (CBL) to enhance light output power of GaN-based light-emitting diodes (LEDs). Nanoimprint lithography (NIL) was used to form patterned CBLs (a diameter of 260 nm, a period of 600, and a height of 180 nm). LEDs (chip size: 300 × 800 µm2) fabricated with no CBL, a conventional SiO2 CBL, and a patterned SiO2 CBL, respectively, exhibited forward-bias ...

Cbl proteins are E3 ubiquitin ligases that are negative regulators of many receptor tyrosine kinases. Cbl-b and c-Cbl contain a ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Despite high sequence identity, Cbl UBA domains display remarkably different ubiquitin-binding properties. Here, we report the crystal structure of th...