Disease relevance of MAD2L2

• Adenovirus ADP protein (E3-11.6K), which is required for efficient cell lysis and virus release, interacts with human MAD2B [1].
• Thus, our results demonstrate that overexpression of MAD2L2 correlates with bad prognosis in colorectal cancer [2].
• Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer [2].
• Impairment of MAD2B-PRCC interaction in mitotic checkpoint defective t(X;1)-positive renal cell carcinomas [3].
• Using colony formation assay, we found that suppression of MAD2B conferred hypersensitivity to a range of DNA-damaging agents, especially DNA cross-linkers, such as cisplatin, and gamma-irradiation [4].

High impact information on MAD2L2

• We here demonstrate that the mitotic checkpoint protein MAD2B interacts with PRCC [3].
• Here we have identified human Rev7 (hRev7)/MAD2B/MAD2L2 as an interaction partner for Elk-1 and demonstrate that hRev7 acts to promote Elk-1 phosphorylation by the c-Jun N-terminal protein kinase (JNK) MAP kinases [5].
• In addition, there was also a significant decrease in cisplatin-induced sister chromatid exchange rate, a marker for homologous recombination-mediated post-replication repair in MAD2B-depleted cells [4].
• These results indicate that MAD2B may be a key factor in regulating cellular response to DNA damage in cancer cells [4].
• In this study, we investigated whether MAD2B played a key role in cellular sensitivity to DNA-damaging anticancer drugs by suppressing its expression using RNA interference in nasopharyngeal carcinoma cells [4].

Biological context of MAD2L2

• While overexpression of hREV7 does not lead to cell cycle arrest, we entertain the possibility that it may act as an adapter between DNA repair and the spindle assembly checkpoint [6].
• Tumors with upregulated MAD2L2 expression had significantly higher numbers of aberrant mitotic figures (anaphase bridges), an indication of chromosomal instability [2].
• We have previously identified MAD2L2 as significantly upregulated in locally restricted colorectal tumors by gene expression profiling [2].
• We conclude that expression changes in mitotic arrest deficiency genes (MAD1, MAD2L1, and MAD2L2) play a role in renal carcinogenesis characterized by multiple numerical chromosome abnormalities [7].
• By a yeast two-hybrid system, ribosomal phosphoproteins P0 and P1 and a putative mitotic checkpoint protein, MAD2B, were found to interact with an active-site mutated trichosanthin (TCS) [8].

Anatomical context of MAD2L2

• Two human A549 cell lines were made that constitutively overexpress MAD2B [1].

Physical interactions of MAD2L2

• Although hREV7 interacts with both hREV1 and hREV3, a stable complex formation of the three proteins was undetectable in vitro [9].

Other interactions of MAD2L2

• Here we describe a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identified in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3) [6].
• Human MAD2B is about 25% identical to human MAD2, a spindle assembly checkpoint protein [1].
• Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7 [9].
• Trichosanthin interacts with acidic ribosomal proteins P0 and P1 and mitotic checkpoint protein MAD2B [8].

Analytical, diagnostic and therapeutic context of MAD2L2

• Northern blot analyses indicate that human MAD2B is expressed ubiquitously [1].
• To address this question, 118 histologically confirmed colorectal lesions were analyzed by quantitative real-time PCR for expression of MAD2L2, and compared to normal colon tissue from 11 patients [2].

References