Antibody study into autophagy reveals new role for HMGB proteins

The HMGB, or high mobility group box proteins in our antibody catalog are used in

a variety of research areas, predominantly histone, chromatin and transcription research. Now, an antibody study has revealed a possible new role for at least one of the HMGB proteins: as a trigger for autophagy, or spontaneous cell death.

HMGB proteins are an important chromosomal repair group, known to also be involved in the transcription, replication and recombination of DNA. They are of interest to antibody suppliers as mutations have been implicated in the formation of benign tumours; HMGB antibodies are also expressed in patients suffering from autoimmune disease.

It seems that at least one HMGB protein - HMGB1 - plays far more than just a passive regulatory and repair role within the cell. It normally resides in the nucleus, altering the DNA to allow transcription factors to interact with other important regulatory proteins. However, in 2007, Sitia et al demonstrated the protein can act as an extracellular chemokine. Hepatic cells damaged by cytotoxic T lymphocytes (CTLs) released HMGB1 into the extracellular fluid, where it recruited inflammatory mononucleocytes and neutrophils to the damaged cells, triggering inflammation and hastening their demise.

In the latest study, Tang et al set out to determine whether HMGB1 also has a role to play in the cytosol (intracellular fluid). It was discovered that although HMGB1 does not normally reside in the ICF, cells stressed by starvation released it there from the nucleus, thus triggering commencement of autophagy. Antibody assays showed that, in response to starvation, the nucleus increased its expression of reactive oxygen species, triggering oxidation of 3 key cysteine domains in HMGB1. This resulted in translocation of the protein to the cytosol, where it bound to Beclin-1, causing it to dissociate from Bcl-2. Normally, the Beclin-1/Bcl-2 complex inhibits autophagy.

The antibody catalogue we at Novus Biologicals produce is widely used in cancer research. It seems HMB1 might have a role to play there too, as tumour cells often trigger autophagy in order to resist the effects of chemotherapy, immunotherapy and other types of treatment.

Antibody study into autophagy reveals new role for HMGB proteins

By: Tom

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