SAFB

SAFB Full Name

scaffold attachment factor B

SAFB Introduction

SAFB (scaffold attachment factor B) is a nuclear matrix-associated protein that links chromatin to the nuclear scaffold and modulates transcription, splicing, and the DNA-damage response. The protein contains an N-terminal SAP domain, a central RNA-recognition motif (RRM), and a C-terminal coiled-coil that mediates dimerization and interactions with multiple partners including SAF-A, hnRNPs, and the estrogen receptor. SAFB maps to chromosome 19p13.3 and gives rise to a related protein, SAFB2, through gene duplication.

Figure 1. The structure of SAFB.

Chromatin Scaffold and Transcriptional Regulator
SAFB binds scaffold/matrix attachment regions (S/MARs) of DNA through its SAP domain and tethers chromatin loops to the nuclear scaffold, thereby organizing higher-order genome architecture. Through its RRM and C-terminal regions, SAFB also binds the estrogen receptor, SR proteins, and hnRNPs, acting as a co-repressor that dampens transcription of estrogen-responsive genes and as a splicing regulator that influences alternative exon inclusion. On DNA damage, SAFB is phosphorylated by ATM and recruits repair factors to damaged chromatin, with its loss leading to prolonged DNA-damage signaling and increased sensitivity to ionizing radiation.

Breast Cancer and Stress Responses
SAFB expression is frequently reduced in estrogen-receptor-positive breast cancers, where its loss correlates with higher tumor grade and with shorter relapse-free survival, consistent with a tumor-suppressor function. Restoration of SAFB in breast cancer cell lines reduces proliferation and blocks estrogen-driven transcription, indicating that SAFB-based interventions could be therapeutically useful in luminal breast cancer. More recently, SAFB has been linked to the integrated stress response through its interactions with the GADD34–PP1 complex, and reduced SAFB expression may sensitize tumor cells to translation-inhibiting therapies.

Alternate Names for SAFB

SAFB; scaffold attachment factor B; HAP; HET; SAFB1; SAF-B1; scaffold attachment factor B1; SAF-B; SAB-B1; HSP27 ERE-TATA-binding protein