Phospho-SP1 (Ser59) Recombinant Rabbit mAb (S-3714-13)

Phospho-Sp1 (Ser59) refers to the phosphorylation of the transcription factor Sp1 at serine residue 59, a post-translational modification that regulates Sp1's transcriptional activity, proteolytic processing, and protein stability. Sp1 contains multiple phosphorylation sites, but Ser59 is notable for being within a Cyclin A/cdk2 consensus motif (QPSP sequence), and its phosphorylation induces removal of the inhibitory domain through proteolytic cleavage, thereby activating Sp1's DNA-binding transcriptional activity. This modification is catalyzed by several kinases: Cyclin A/cdk2 phosphorylates Ser59 upon S-phase entry, which is necessary for subsequent recognition, ubiquitination, and degradation of Sp1 by the SUMO-targeted E3 ubiquitin ligase RNF4, a process required for removing Sp1 and 53BP1 from DNA double-strand breaks to permit homologous recombination. Senescence-associated ERK1/2 (SA-pErk1/2), downstream of PKCα activated by reactive oxygen species, also phosphorylates Sp1 specifically at Ser59 in vivo (but not threonine residues) during cellular senescence, enhancing p21Sdi1 transcription and contributing to cell cycle arrest. Additionally, aPKC-ι directly phosphorylates Sp1 at Ser59 to increase Sp1 binding to the Snail promoter, promoting epithelial-mesenchymal transition and immunosuppression in cholangiocarcinoma cells.