BTF3

BTF3 Full Name

basic transcription factor 3

BTF3 Introduction

BTF3 (basic transcription factor 3) is a highly conserved protein that was originally identified as a general transcription factor required for RNA polymerase II–driven transcription initiation from TATA-box-containing promoters. Subsequent work showed that BTF3 also functions outside of basal transcription, serving as a nascent-polypeptide-associated complex (NAC) component that supports ribosome biogenesis and protein-folding at the ribosome exit tunnel. The BTF3 gene maps to chromosome 5q13.2 and produces two main isoforms, BTF3a and BTF3b, that differ in their N-terminal extensions.

Figure 1. The structure of BTF3.

Transcription Initiation and Ribosome-Associated Chaperone Activity
BTF3 forms a heterodimer with BTF3-like (BTF3L/NACβ) to create the nascent-polypeptide-associated complex (NAC), which associates with the ribosome near the peptide exit tunnel and helps fold newly synthesized proteins. Within the nucleus, BTF3 contributes to the assembly of the pre-initiation complex at TATA-box-containing promoters, where it cooperates with TBP and TFIID. Through its dual roles in ribosome-associated folding and transcription, BTF3 couples the production of nascent polypeptides to the expression of their cognate transcripts, ensuring proteostatic balance in proliferating cells.

Cancer and Stem Cell Function
BTF3 is overexpressed in several cancers, including breast, prostate, and pancreatic cancer, where it supports tumor cell proliferation through its ribosome-associated chaperone activity. In embryonic stem cells, BTF3 is required for pluripotency maintenance, and its depletion triggers spontaneous differentiation. These observations have prompted interest in BTF3 as a candidate target in cancer therapy, although the protein's ubiquitous expression and essential function make selective inhibition challenging. BTF3 expression levels are being evaluated as a prognostic biomarker in several solid tumor types.

Alternate Names for BTF3

BTF3; basic transcription factor 3; NACB, nascent polypeptide associated complex beta polypeptide; transcription factor BTF3; BTF3a; BTF3b; RNA polymerase B transcription factor 3; nascent-polypeptide-associated complex beta polypeptide; NACB; BETA-NAC;