PBX2

What is PBX2 protein?

PBX2 (PBX homeobox 2) gene is a protein coding gene which situated on the long arm of chromosome 6 at locus 6p21. PBX2 is a protein that belongs to the PBX family of homeodomain transcription factors. These proteins are known to serve as DNA-binding partners for a subset of Hox transcription factors and are involved in various cellular processes, including development and differentiation. PBX2 specifically is involved in the regulation of gene expression and has been associated with several biological functions and diseases. The PBX2 protein is consisted of 430 amino acids and its molecular mass is approximately 45.9 kDa.

What is the function of PBX2 protein?

PBX2 acts as a cofactor that can bind to specific DNA sequences and regulate the transcription of target genes. PBX2 plays a role in embryonic development and is involved in the development of various tissues and organs. It is expressed in a variety of tissues and is thought to be important for normal cellular differentiation and development. PBX2 has been shown to play a role in the immune system, potentially influencing the activity of immune cells and the innate immune response. The protein is involved in basic cellular processes, cell proliferation, and transcription regulation, which are essential for maintaining normal cell function and preventing uncontrolled cell growth.

PBX2 Related Signaling Pathway

BX2 serves as a DNA-binding partner for a subset of Hox transcription factors, which play a critical role in the development of the body plan and the specification of the main axes of the embryo. These interactions are part of the transcriptional regulation pathways. PBX2 has been shown to act as a cofactor that regulates numerous genes, potentially influencing various signaling pathways through its effects on gene expression. PBX2 has been implicated in the immune system, possibly playing a role in the innate immune response through its interactions with other proteins and transcription factors. While not directly mentioned in the provided resources, given its role as a transcription factor, PBX2 may indirectly influence metabolic pathways by regulating the expression of genes involved in these processes.

PBX2 Related Diseases

PBX2 (PBX Homeobox 2) is a gene that encodes a protein involved in various biological processes. Mutations or altered expression of this gene has been associated with several diseases: Partial Trisomy Distal 4Q is a chromosomal disorder characterized by the presence of an extra part of chromosome 4. This condition can lead to developmental delays, intellectual disability, and other health issues. PBX2 has been implicated in certain types of leukemia, particularly in the context of chromosomal translocations that involve the PBX2 gene, such as the t(1;19) translocation in acute lymphoblastic leukemia (ALL). Recent research suggests that PBX2 may also play a role in solid tumors, potentially through its effects on cell growth and differentiation. For example, low PBX2 expression has been associated with better prognosis in esophageal squamous cell carcinoma (ESCC) patients. While not directly mentioned in the provided resources, given the role of PBX2 in transcriptional regulation, it may indirectly influence metabolic pathways by regulating the expression of genes involved in these processes.

Bioapplications of PBX2

Given its role in cellular differentiation and development, PBX2 could potentially be a target for gene therapy approaches, particularly in conditions where its expression is aberrant. PBX2's association with certain diseases suggests it could serve as a diagnostic marker. Detecting changes in PBX2 expression levels could help in the early diagnosis or stratification of patients for more personalized treatment. PBX2 is involved in cell fate decisions, making it an important factor in stem cell research and regenerative medicine.

Case Study 1: Jianjiao Lin, 2021

HOXA6 gene plays a role of the oncogene in various cancers. Nonetheless, its effect on gastric cancer (GC) occurrence and development is still unclear. The researchers analysed whether HOXA6 interacts with the PBX2 protein using the STRING database. The molecular mechanism by which HOXA6 synergizes with PBX2 in GC metastasis is not fully understood. Here, the expression of HOXA6 was increased in GC tissues and cell lines. The upregulation of HOXA6 was closely associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients based on tissue microarray (TMA) data. Moreover, the overexpression of HOXA6 promoted, whereas siRNA-mediated repression of HOXA6 inhibited, the cell proliferation, migration, and invasion of GC cells. Furthermore, HOXA6 could physically interact with and stabilize PBX2. In addition, HOXA6 and PBX2 expression was positively correlated in GC cells and tissue. HOXA6 and PBX2 suppression in GC cells also led to decreased migration and invasion potential in vitro. In vivo, HOXA6 was shown to cooperate with PBX2 to enhance cell metastasis via orthotopic implantation.

Fig1. HOXA6-Flag was co-transfected with PBX2-HA into AGS and BCG-823 cells.

Fig2. Western blot analysis was is used to determinate the expression of HOXA6 and PBX2 in GC cell lines.

Case Study 2: Elena Longobardi, 2003

To bind DNA and to be retained in the nucleus, PBX proteins must form heterodimeric complexes with members of the MEINOX family. Therefore the balance between PBX and MEINOX must be an important regulatory feature. The researchers show that overexpression of PREP-1 influences the level of PBX-2 protein maintaining the PREP-1-PBX balance. This effect has important functional consequences. F9 teratocarcinoma cells stably transfected with PREP-1 had an increased DNA binding activity to a PREP-PBX-responsive element. Because PREP-1 binds DNA efficiently only when dimerized to PBX, the increased DNA binding activity suggests that the level of PBX might also have increased. Indeed PREP-1-overexpressing cells had a higher level of PBX-2 and PBX-1b proteins. PBX-2 increase did not depend on increased mRNA level or a higher rate of translation but rather because of a protein stabilization process. Indeed, PBX-2 level drastically decreased after 3 h of cycloheximide treatment in control but not in PREP-1-overexpressing cells and the proteasome inhibitor MG132 prevented PBX-2 decay in control cells.

Fig3. Immunoblotting analysis of PREP-1 and PBX proteins.

Fig4. Overexpression of PREP-1 induces an increase of PREP-1-PBX DNA binding activity.

PBX2 has several biochemical functions, for example, chromatin binding,protein binding,sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PBX2 itself. We selected most functions PBX2 had, and list some proteins which have the same functions with PBX2. You can find most of the proteins on our site.

PBX2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PBX2 here. Most of them are supplied by our site. Hope this information will be useful for your research of PBX2.

HOXA1;CARD9;PKNOX1;CCDC88B;DCTN3;IKBKAP;TLX1;RPL4;NUP62;SKIV2L2;BLOC1S1;COPS6;q81jv7_bacan