SDCBP2 Human

What is SDCBP2 and what are its alternative nomenclatures?

SDCBP2 (syndecan binding protein 2) is a human protein also known as Syntenin-2. Alternative names include SITAC, SITAC18, ST-2, and ST2. The protein is encoded by the SDCBP2 gene located on chromosome 20p13 in humans . It belongs to a family of adaptor proteins that contain PDZ domains and plays significant roles in cell signaling, cell adhesion, and intracellular trafficking pathways .

SDCBP2 contains two class II PDZ domains that facilitate protein-protein interactions by binding to the cytoplasmic C-terminus of transmembrane proteins . These interactions are crucial for mediating cell signaling and organizing protein complexes. The protein exists in two alternatively spliced variants, 2alpha and 2beta, which differ in the lengths of their N-terminal regions .

What is the cellular localization of SDCBP2 and how does this relate to its function?

SDCBP2 exhibits a dynamic subcellular distribution pattern primarily in the cytoplasm and plasma membrane . This localization pattern is consistent with its function as an adaptor protein that mediates protein-protein interactions. The protein binds to phosphatidylinositol 4,5-bisphosphate (PIP2) and plays a critical role in nuclear PIP2 organization and cell division .

Researchers investigating SDCBP2 localization should consider using subcellular fractionation techniques combined with immunodetection methods. Immunohistochemistry data from the PACO41054 antibody shows that SDCBP2 can be detected in both human breast cancer tissue and liver tissue, suggesting tissue-specific expression patterns that may correlate with its various functions .

What antibodies and detection methods are available for SDCBP2 research?

Several validated antibodies are available for SDCBP2 detection. The SDCBP2 Polyclonal Antibody (PACO41054) is a well-characterized tool produced in rabbits that has been validated for Western blotting, ELISA, and immunohistochemistry applications . This antibody has high specificity for human samples and has been successfully used for detecting SDCBP2 in various tissue types, including breast cancer and liver tissue.

For immunohistochemistry applications, the recommended dilution range is 1:20-1:200, with optimal results typically achieved at 1:100 dilution . For ELISA applications, dilutions ranging from 1:2000 to 1:10000 are recommended .

The antibody recognizes a recombinant human Syntenin-2 protein fragment (amino acids 11-207) and is supplied as a liquid in a storage buffer containing 0.03% Proclin 300, 50% Glycerol, and 0.01M PBS at pH 7.4 .

What are the methodological considerations for quantitative assessment of SDCBP2 expression?

For quantitative analysis of SDCBP2 expression, several methodological approaches are available:

• ELISA-based quantification: Commercial ELISA kits, such as the Human Syntenin-2 (SDCBP2) ELISA Kit, offer a reliable method for quantitative determination of SDCBP2 levels in research samples . These assays typically employ a sandwich ELISA format where an antibody specific for SDCBP2 is pre-coated onto a microplate. Standards and samples are then added, and any SDCBP2 present binds to the immobilized antibody. After washing, an HRP-conjugated detection antibody specific for SDCBP2 is added, followed by a chromogenic substrate to produce a color signal proportional to the amount of bound SDCBP2 .

• Western blotting: This technique provides semi-quantitative assessment of SDCBP2 protein levels and can reveal information about post-translational modifications.

• qRT-PCR: For measuring SDCBP2 mRNA expression levels, quantitative PCR approaches can be employed.

When analyzing SDCBP2 expression in clinical samples, researchers should consider establishing appropriate cutoff values for categorizing "high" versus "low" expression. In gastric cancer research, for instance, studies have employed such stratification to correlate SDCBP2-AS1 expression with clinical outcomes .

What is the role of SDCBP2 in cancer progression and metastasis?

SDCBP2 has been implicated in cancer progression, metastasis, and tumor growth, making it a promising target for cancer research . Its function as an adaptor protein that mediates cell signaling, adhesion, and trafficking contributes to its potential role in cancer development.

Research indicates that SDCBP2 may be regulated by human papillomavirus (HPV), with both HPV8 and HPV16 controlling SDCBP2 at the mRNA level . This finding suggests a potential role for SDCBP2 in HPV-associated carcinogenesis.

Interestingly, while SDCBP2 itself may promote cancer progression, its antisense RNA (SDCBP2-AS1) appears to act as a tumor suppressor in gastric cancer. Studies have shown that SDCBP2-AS1 is significantly downregulated in gastric cancer tissues and its low expression correlates with poor patient prognosis .

How does SDCBP2-AS1 regulate gastric cancer progression through β-catenin signaling?

SDCBP2-AS1, an antisense RNA of SDCBP2, plays a significant role in suppressing gastric tumorigenicity and metastasis. Research has revealed the following mechanistic pathway:

• SDCBP2-AS1 physically binds to heterogeneous nuclear ribonucleoprotein K (hnRNP K) .

• This binding represses SUMOylation of hnRNP K and facilitates ubiquitination of both hnRNP K and β-catenin .

• Enhanced ubiquitination promotes the degradation of β-catenin in the cytoplasm .

• When SDCBP2-AS1 is silenced, SUMOylation of hnRNP K increases, which stabilizes β-catenin activity .

• Stabilized β-catenin alters transcription of downstream genes, resulting in tumorigenesis and metastasis of gastric cancer .

This mechanism reveals a complex post-translational regulation network involving SDCBP2-AS1, hnRNP K, and β-catenin that significantly impacts gastric cancer development.

The clinical relevance of SDCBP2-AS1 expression in gastric cancer patients is highlighted in the following table:

This data demonstrates that SDCBP2-AS1 expression correlates with specific clinical parameters, including gender and tumor size .

What protein-protein interactions does SDCBP2 participate in?

SDCBP2 contains two class II PDZ domains that facilitate protein-protein interactions by binding to the cytoplasmic C-terminus of transmembrane proteins . These interactions are essential for cell signaling and the organization of protein complexes.

Key interactions include:

• Binding to phosphatidylinositol 4,5-bisphosphate (PIP2): SDCBP2 binds to PIP2 and contributes to nuclear PIP2 organization .

• Protein dimerization: SDCBP2 has been shown to participate in both homodimerization (with itself) and heterodimerization (with other proteins) .

• Protein C-terminus binding: The PDZ domains of SDCBP2 interact with the C-terminal portions of various transmembrane proteins, facilitating signaling and trafficking functions .

Understanding these protein-protein interactions is crucial for deciphering the molecular mechanisms through which SDCBP2 influences cellular processes and potentially contributes to disease states.

How can researchers effectively study SDCBP2 interactions experimentally?

To investigate SDCBP2 interactions, researchers can employ several complementary approaches:

• Co-immunoprecipitation (Co-IP): This technique can identify protein complexes containing SDCBP2 in native conditions. Using antibodies like PACO41054, researchers can pull down SDCBP2 and identify interacting partners by mass spectrometry or Western blotting .

• GST pull-down assays: Recombinant GST-tagged SDCBP2 can be used to identify direct protein-protein interactions in vitro.

• Yeast two-hybrid screening: This approach can identify novel interaction partners of SDCBP2.

• Proximity labeling techniques (BioID or APEX): These methods can reveal the proximal proteome of SDCBP2 in living cells.

• RNA-protein interaction studies: As demonstrated with SDCBP2-AS1 and hnRNP K, RNA pull-down assays can be used to investigate RNA-protein interactions involving SDCBP2 or its related transcripts .

For genetic manipulation studies, researchers have successfully used shRNA approaches to silence SDCBP2-AS1 expression and observed effects on cell proliferation and migration both in vitro and in vivo . Similar approaches can be applied to study SDCBP2 function directly.

How can contradictory findings about SDCBP2 function be reconciled in different experimental contexts?

When encountering contradictory findings regarding SDCBP2 function, researchers should consider the following factors:

• Cellular context: SDCBP2 function may vary depending on cell type. For instance, its role in normal cells might differ from that in cancer cells.

• Experimental conditions: Different experimental approaches (in vitro vs. in vivo, overexpression vs. knockdown) might yield apparently contradictory results.

• Isoform-specific effects: The two alternatively spliced variants, 2alpha and 2beta, might have distinct functions .

• Post-translational modifications: Modifications like SUMOylation and ubiquitination can significantly alter protein function, as demonstrated in the regulatory network involving SDCBP2-AS1, hnRNP K, and β-catenin .

• Interaction with antisense transcripts: The relationship between SDCBP2 and its antisense transcript SDCBP2-AS1 adds complexity to interpreting experimental results .

To reconcile contradictory findings, researchers should design experiments that systematically address these variables, using multiple complementary approaches and carefully validating results across different experimental systems.

What are promising therapeutic strategies targeting SDCBP2 in human diseases?

Based on its involvement in cancer progression and cellular signaling, several therapeutic strategies targeting SDCBP2 show promise:

• Small molecule inhibitors: Developing compounds that disrupt SDCBP2 PDZ domain interactions could modulate its signaling functions.

• Antisense oligonucleotides: Given the role of SDCBP2-AS1 in suppressing gastric cancer, antisense approaches targeting SDCBP2 might have therapeutic potential .

• Restoration of SDCBP2-AS1 expression: In gastric cancer, where SDCBP2-AS1 is downregulated, strategies to restore its expression might suppress tumor growth and metastasis .

• Targeting the SDCBP2-hnRNP K-β-catenin axis: Disrupting this regulatory network could be effective in cancers where this pathway contributes to pathogenesis .

• Combination therapies: Targeting SDCBP2 in combination with other therapeutic approaches might enhance efficacy.

When developing SDCBP2-targeted therapies, researchers should carefully consider potential off-target effects, given the protein's involvement in fundamental cellular processes and its structural similarity to other PDZ domain-containing proteins.