PAX7

What is PAX7 Protein?

PAX7 is a transcription factor protein, meaning it helps control the activity of certain genes. It plays a big role in developing the neural crest and gastrulation, processes crucial for forming the nervous system and other tissues during embryonic growth. PAX7 is involved in muscle development, helping regulate the proliferation of muscle precursor cells. It's also found in rare spermatogonial stem cells in the testis, but interestingly, it's not essential for fertility. In clinical contexts, PAX7 has implications in tumor suppression, particularly linked to a type of cancer called alveolar rhabdomyosarcoma. This protein has different variants due to alternative splicing, but their full biological significance isn't yet clear.

What is the Function of PAX7 Protein?

PAX7 is a transcription factor that primarily aids in the development and function of various tissue types in the body. It plays a critical role in neural crest development, myogenesis, and muscle tissue regeneration. This protein influences the expression of several neural crest markers essential for early embryonic development. It's also pivotal in regulating the proliferation of muscle precursor cells, thereby contributing to muscle growth and repair. Moreover, PAX7 marks a unique type of spermatogonial stem cells, indicating its significance in maintaining a pool of germline stem cells in the testis. Interestingly, it's not essential for spermatogenesis since mice lacking PAX7 don't suffer from fertility issues. Additionally, PAX7 has a role in recovery post radiation or chemotherapy, as these PAX7-positive cells survive such treatments and help in tissue recovery.

PAX7 Related Signaling Pathway

PAX7 is linked to several signaling pathways that are crucial for its role in tissue development and regeneration. One key aspect of PAX7 involves its cooperation with other genes like PAX3, forming heterodimers to influence cell differentiation and proliferation. These interactions help initiate pathways significant for muscle development, such as those involving muscle precursor cells. Moreover, PAX7's interaction with other proteins connects it to signaling mechanisms that are vital for maintaining the balance of stem cells in tissues like muscle and testis. Despite its widespread influence, the exact signaling pathways PAX7 engages in continue to be a subject of research, with ongoing studies aiming to clarify these complex interactions.

PAX7 Related Diseases

PAX7 has clinical importance, mainly in the context of specific diseases. One significant area where PAX7 is linked is in cancer growth, particularly in alveolar rhabdomyosarcoma, a type of cancer that affects muscle tissue. This link arises because PAX7 can form a fusion gene with another gene, leading to tumor formation. Beyond cancer, animal studies have shown that mutations in PAX7 can cause developmental issues such as defects in the maxilla and nose. While the exact role of PAX7 in humans for other diseases isn't fully understood, its interaction with various cellular processes makes it a vital area of study in medical genetics.

Bioapplications of PAX7

PAX7 has several bioapplications, especially in the field of regenerative medicine and stem cell research. It's widely used as a marker to identify and isolate satellite cells, which are essential for muscle regeneration. This capability makes PAX7 crucial in studies aimed at understanding muscle diseases and potential therapies for muscle repair. Additionally, its role in neural crest development makes it significant in neurobiology research, offering insights into neural disorders and development. Researchers also explore PAX7 in cancer studies due to its involvement in certain tumor growths, providing pathways for developing targeted cancer treatments.

Case Study 1: Skrzypek K. et al. Cells. 2021

Rhabdomyosarcoma (RMS) is a common children's tumor caused by differentiation issues. Studying RH30 cell subclones, one without PAX7 and one with it, revealed differences in growth, migration, and tumor traits. These subclones, with the same STR profile, varied in adhesion molecules and transcription factors like MYOD and ID. PAX7 silencing with siRNA confirmed its key role in RMS progression, indicating that PAX7 and ID are crucial in RMS development.

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  Fig1. PAX7+ positive cells proliferated faster in standard growth medium.
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  Fig2. RH30 PAX7− cells displayed higher level of CXCR4 receptor evaluated with flow cytometry.

Case Study 2: Kim H. et al. Stem Cell Reports. 2021

Inducing PAX7 in stem cells creates muscle progenitors useful for repairing dystrophic muscles. While lentiviral vectors are common for this, targeting PAX7 to genomic safe harbor (GSH) sites is another option. This GSH method produces progenitors with good expansion and engraftment, offering a potential alternative for muscle therapy.

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  Fig3. Southern blot shows integration of PAX7 and rtTA transgenes.
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  Fig4. Bar graphs show expression analysis of total, exogenous, and endogenous PAX7 in LV and GSH myogenic progenitors.

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  Fig1. Schematic diagram of the TGF-β superfamily-induced transcriptional activation pathways involved in the establishment of RAD52-dependent ALT. (Eunji Choi, 2024)
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  Fig2. T therapy reduced adipogenic machinery and enhanced Myogenic gene machinery. (Siresha Bathina, 2024)

PAX7 has several biochemical functions, for example, sequence-specific DNA binding,transcription factor activity, RNA polymerase II core promoter sequence-specific,transcription factor activity, sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PAX7 itself. We selected most functions PAX7 had, and list some proteins which have the same functions with PAX7. You can find most of the proteins on our site.

Function	Related Protein
sequence-specific DNA binding	HOXA11A,ZNF498,DBX1A,SOX30,SOX7,WT1,SIX9,NKX3.3,TSN,ATF4B2
transcription factor activity, sequence-specific DNA binding	CEBPB,SIX1,ZFP12,CEBP1,AFF4,ARNTL1A,ZNF397,LHX8A,SLAMF7,INSM1A
transcription factor activity, RNA polymerase II core promoter sequence-specific	SMAD3,HEY2,TFAP2B,HEYL,HEY1,MAX,NKX3,MEF2C

PAX7 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 PAX7 here. Most of them are supplied by our site. Hope this information will be useful for your research of PAX7.

Dlg4;FYN;SRC;AKR1B1;NCK1;CRK