COBRA1: A Key Player in Transcriptional Pausing

Co-factor of BRCA1, also known as COBRA1, was first identified as a protein that binds to the tumour suppressor protein encoded by the breast cancer susceptibility gene BRCA1 (1). It was subsequently found to be identical to subunit B of the Negative Elongation Factor (NELF) complex (2). NELF is composed of four subunits (A, B, C or D, and E) and plays a pivotal role in the transcriptional pausing of RNA polymerase II.

Broadly speaking there are three main steps to transcription – initiation, elongation and termination. Each step is tightly controlled, with NELF being one of the major factors to regulate elongation. NELF and DSIF (DRB-Sensitivity Inducing Factor) bind to RNA Polymerase II once it is downstream of the promoter sequence of the target gene, which results in transcriptional pausing. Various activators of transcription are subsequently involved in recruiting Positive Transcription Elongation Factor (P-TEFb) to RNA Polymerase II, leading to the dissociation of NELF and allowing elongation to occur (3). It has been postulated that transcriptional pausing is a critical checkpoint to ensure that RNA Polymerase II is fully matured prior to the start of elongation (4). Another theory is that transcriptional pausing serves to keep promoters in a poised state that is amenable to rapid stimulation by environmental or developmental cues (5).

COBRA1 is believed to play roles in cell proliferation, differentiation, apoptosis and oncogenesis. Amleh et al have used COBRA1 antibodies to demonstrate a reduction in COBRA1 expression levels following the treatment of mouse embryonic stem cells with COBRA1 RNAi, in a study to illustrate the role of COBRA1 in early embryogenesis (6). Sun et al have used COBRA1 antibodies to quantify the levels of COBRA1 and BRCA1 in stable knockdown cell lines, in a study to show that these two genes may be involved in common gene regulatory pathways to suppress breast cancer progression (1).

Immunohistochemistry-Paraffin: COBRA1 Antibody [NBP2-15935] - Nucleus on gastric carcinoma; antibody dilution: 1:500.