Biomedical subjects

Ehud Razin

Publications and source records attributed to Ehud Razin.

4 recordsLinked to original sources

PubMed2003

A novel strategy using single-chain antibody to show the importance of Bcl-2 in mast cell survival.

Apoptosis or programmed cell death plays an important role in a wide variety of physiologic processes and is regulated by proteins of the Bcl-2 family consisting of both antiapoptotic and proapoptotic factors. The direct involvement of the Bcl-2 protein family in the process of mast cell apoptosis has not been clarified. In the present work we have used a single-chain antibody (scFv) raised against Bcl-2 derived from a semisynthetic human phage-display antibody library. The addition of TAT sequence, which is responsible for translocation through the membrane, endows the anti-Bcl-2-scFv with the ability to penetrate living cells. Moreover, it specifically neutralizes Bcl-2 intracellularly by binding to the BH1 domain and eradicates its antiapoptotic activity in 2 types of mast cells and in a human breast cancer cell line.

Amino Acid Sequence↗

PubMed2002

The function of MITF and associated proteins in mast cells.

Mutation of microphthalmia transcription factor (MITF) results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. The primary cell types affected in MITF-deficient mice are melanocytes, osteoclasts and mast cells. A search for MITF-associated proteins, using a mast cell library that was screened with a construct that encodes the basic helix-loop-helix leucine zipper (bHLH-Zip) domain of MITF, resulted in the isolation of the protein kinase C interacting (PKCI) protein 1 and protein inhibitor of activated STAT3 (PIAS3). We have accumulated clear evidence of a function for these two proteins as repressors of MITF-induced transcriptional activity. Here, we describe this evidence and ideas that give some insight into the cellular network of interactions between various transcription factors and MITF.

Animals↗

PubMed2001

A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor.

In vitro and in vivo evidence suggest that microphthalmia transcription factor (MITF) plays a key regulatory role in tissue-specific gene regulation in several cell types, including melanocytes, osteoclasts, and mast cells. A yeast two-hybrid search, using a portion of a nonmutated MITF gene as the bait in the screening of a mast cell library, resulted in the isolation of the STAT3 inhibitor, PIAS3. PIAS3 is a transcriptional inhibitor that acts by specifically inhibiting STAT3's DNA binding activity. We found that it can directly associate with MITF using an in vitro pull-down assay. Immunoprecipitation of MITF from rat basophilic leukemic cells or mouse melanocytes resulted in the specific co-immunoprecipitation of PIAS3. Co-transfection of MITF with PIAS3 in NIH 3T3 fibroblasts containing an mMCP-6 promoter-luciferase reporter demonstrated up to 94% inhibition of MITF-mediated transcriptional activation. Using a gel-shift assay, it was shown that PIAS3 can block DNA binding activity. It was also found that STAT3 does not interfere, either in vitro or in vivo, with the interaction between PIAS3 and MITF. These data suggest that PIAS3 functions in vivo as a key molecule in supressing the transcriptional activity of MITF, a role of considerable importance in mast cell and melanocyte development.

3T3 Cells↗

PubMed2000

Mast Cell-Nerve Interactions.

Mutual associations between nerves and mast cells have been observed in normal conditions and in pathological ones such as human irritable bowel syndrome, atopic dermatitis, interstitial cystitis, and more. Here we review the recent literature in this field, putting emphasis on the enteric, skin, and urinary systems, and the pathophysiological implications of this interaction in them.

Journal Article↗