This subfamily corresponds to the RRM1 of PARP-14, also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs. Moreover, the absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis. Research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. PARP-14 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.
Jiyao W et al.(2023). "The conserved domain database in 2023.",