The molecular basis for the development of adult T-cell leukemia/lymphoma in patients with an IRF4^K59R mutation.

ABSTRACT: Interferon regulatory factor 4 (IRF4) is an essential regulator in the development of many immune cells, including B- and T-cells and has been implicated directly in numerous hematological malignancies, including adult T-cell leukemia/lymphoma (ATLL). Recently, an activating mutation in the DNA-binding domain of IRF4 (IRF4^K59R ) was found as a recurrent somatic mutation in ATLL patients. However, it remains unknown how this mutation gives rise to the observed oncogenic effect. To understand the mode of IRF4^K59R -mediated gain of function in ATLL pathogenesis, we have determined the structural and affinity basis of IRF4^K59R /DNA homodimer complex using X-ray crystallography and surface plasmon resonance. Our study shows that arginine substitution (R59) resul

SUBMITTER: Sundararaj S 

PROVIDER: S-EPMC8927869 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature