STK11 Protein, Human (His-SUMO)

STK11 Protein, a tumor suppressor serine/threonine-protein kinase, intricately regulates the activity of AMP-activated protein kinase (AMPK) family members, exerting influence over diverse cellular processes including metabolism, cell polarity, apoptosis, and the DNA damage response. Operating through the phosphorylation of the T-loop of AMPK family proteins, such as PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3, and SNRK, STK11 facilitates their activation while excluding MELK. Beyond the AMPK family, STK11 extends its regulatory reach to non-AMPK proteins like STRADA, PTEN, and possibly p53/TP53. Functioning as a pivotal upstream regulator of AMPK, STK11 orchestrates cellular responses including the inhibition of growth-promoting signaling pathways during low energy conditions, maintenance of glucose homeostasis in the liver, initiation of autophagy in nutrient-deprived cells, and facilitation of B-cell differentiation in the germinal center in response to DNA damage. Additionally, STK11 plays a crucial role in cellular polarity by remodeling the actin cytoskeleton and is essential for cortical neuron polarization through the phosphorylation and activation of BRSK1 and BRSK2. In the realm of DNA damage response, STK11 interacts with p53/TP53, participating in transcription activation on the CDKN1A/WAF1 promoter, and acts as a mediator of p53/TP53-dependent apoptosis. Furthermore, STK11 is implicated in UV radiation-induced DNA damage response by phosphorylating CDKN1A in collaboration with NUAK1, contributing to its degradation for optimal DNA repair, and it also plays a role in spermiogenesis.