Lys-63-specific deubiquitinase BRCC36 is a crucial enzyme involved in the regulation of ubiquitination, a process that tags proteins for degradation or other cellular functions. BRCC36 is part of the BRCA1-A complex, which includes RAP80, CCDC98/ABRAXAS, BRCC45/BRE, MERIT40/NBA1, BRCC36, and BRCA1 . This complex specifically recognizes and removes Lys-63-linked ubiquitin chains from histones H2A and H2AX at DNA damage sites, facilitating the recruitment of the BRCA1-BARD1 heterodimer to double-strand breaks (DSBs) in DNA .
BRCC36 plays a significant role in maintaining genomic stability by participating in DNA repair processes. It is a member of the JAMM/MPN+ family of zinc metalloproteases, which are known for their ability to cleave Lys-63-linked polyubiquitin chains . This specific activity is crucial for the regulation of protein degradation and signaling pathways within the cell.
Recent studies have highlighted the importance of BRCC36 in the context of multiple myeloma (MM), a type of hematological malignancy. BRCC36 has been shown to enhance the sensitivity of MM cells to lenalidomide, an immunomodulatory drug (IMiD), by inhibiting the lysosomal degradation of cereblon (CRBN) . CRBN is a substrate receptor of the cullin 4-RING E3 ligase (CRL4) complex, which promotes the ubiquitination and degradation of target proteins, thereby inhibiting the proliferation of myeloma cells .
Biochemical experiments have demonstrated that BRCC36, within the BRISC complex, protects CRBN from lysosomal degradation by specifically cleaving the K63-linked polyubiquitin chain on CRBN . This protection allows for the upregulation of CRBN, enhancing the efficacy of lenalidomide in treating multiple myeloma .
Mouse anti-human antibodies are secondary antibodies generated by immunizing mice with human immunoglobulins. These antibodies are affinity-purified and have well-characterized specificity for human immunoglobulins, making them useful in various detection, sorting, and purification applications . Secondary antibodies offer increased versatility and sensitivity through signal amplification, as multiple secondary antibodies can bind to a single primary antibody .
Mouse anti-human antibodies are commonly used in techniques such as ELISA, Western Blot, Flow Cytometry, and Immunohistochemistry . They can be conjugated with various labels, such as HRP, AP, fluorescence, or biotin, to facilitate detection and analysis .