Serine/threonine kinase that regulates several signal transduction pathways (   ). Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes . Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription . Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1 . Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins . Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 . Blocks the phosphorylation of ERK in response to ERBB2 and HRAS . Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant .
Phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity.
Subcellular locations: Cytoplasm, Endoplasmic reticulum membrane, Mitochondrion membrane, Nucleus envelope
Subcellular locations: Cytoplasm, Nucleus
Isoform 1 and isoform 2 are expressed in various tumor cell lines. Expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis.