Homeodomain-interacting protein kinase 2 (HIPK) 2 is a nuclear serine / threonine kinase that acts as a cofactor and is widely involved in transcriptional regulation. HIPKZ is located in nuclear plaques. With the help of SplooTP53lNPIS, HIPKZ can phosphorylate the 46-position serine of p53, accelerate the acetylation of p53, antagonize the inhibitory effect of M1) MZ on p53, and strengthen p53 function. Through phosphorylation, HIPKZ accelerates the degradation of CtBP and C-Myb by the proteasome, causing cells to undergo apoptosis or differentiation independent of p53. Many tumor cells have low expression of HIPKZ, suggesting that HIPKZ may be an important tumor suppressor gene.
In 1998, Kim et al. Discovered a new nuclear protein kinase family by yeast two-hybrid using a part of mouse Nkx-2 homologous protein a (110-305) as bait. This family of proteins has a conserved kinase domain and a homologous protein interaction domain. Because it can enhance the transcriptional activity of homologous proteins, it is named a homologous domain interaction protein kinase. It is known that there are three members in this family, namely HIPKI, HIPKZ and HIPK3. In 2000, Hofmann et al cloned human HIPKZ, and determined that human HIPKZ was located on chromosome 7q32-q34 by immunofluorescence in situ hybridization, and mouse was chromosome 6B. HIPKZ is highly conserved from beautiful nematodes to humans, and the amino acid sequence between mouse and human is 98% homologous. HIPKZmRNA is generally underexpressed in human tissues in addition to high expression in neural tissues. HIPKZ has 4 transcripts: 1.4kb, 4.skb, 7.skb, and llkb, mainly llkb, and the expression varies from organization to organization.
HIPKZ contains 1189 amino acids and belongs to the DYRK kinase family. The amino terminus is 192-52. The amino acid residue at position 1 is a protein kinase motif, 583-798 are homology domain interaction domains, 839-934 are PEST regions, and the shuttle end is rich in tyrosine and histidine (YH domain). HIPKZ's 221 lysine is highly conserved and is extremely important in the binding of the kinase motif to ATP. Once mutated, the kinase activity is completely lost. In addition, wild-type HIPKZ can be phosphorylated, while kinase-deprived HIPKZ is rarely phosphorylated, suggesting that wild-type HIPKZ is likely to be autophosphorylated.
Wang et al. found by Northern hybridization that compared with normal hematopoietic tissues, the expression of HIPZ in leukemia cell lines H-60, K-562 and MOLT-4 and Burkitt lymphoma cell lines Riaj and Daudi were reduced. Pierantoni et al. Found that the expression of HIPKZ in 8 of 14 thyroid cancer samples and 8 of 20 breast cancers was reduced by 23/-9/10 compared with normal counterparts by RT-PCR in 28 months. Patients with leukemia and myelodysplastic syndrome are often accompanied by a loss of 7 or 7q-1, especially 7q31-7q35. Prompt HIPKZ deletion may play a role in the development of some tumors.
Studies have found that HIPKZ can bind to TRADD and Ran proteins and participate in the phosphorylation of serine STAT3727 and high mobility protein group (HMG). The significance of these effects is unclear. In addition, Harada et al. Found that HIPKZ can directly bind to co-suppressor C-Sik and co-activator Smad1, and inhibit Smadl/4-dependent transcription and bone morphogenetic protein (BMp) -induced alkaline phosphatase transduction.
