المؤلفون: Vattem, Chaitanya¹ (AUTHOR), Pakala, Suresh B¹ (AUTHOR) pakalasb@iisertirupati.ac.in

المصدر: Journal of Biosciences. 4/15/2022, Vol. 47 Issue 2, p1-23. 23p.

مصطلحات موضوعية: *DNA repair, *CELLULAR signal transduction, *DNA damage, *PROTEINS, *CELL proliferation, *CANCER cells, *CELL migration

مستخلص: Metastasis-associated protein 1 (MTA1) is an emerging transcriptional co-regulator and was found to be aberrantly expressed in different types of cancers. MTA1 has been reported to regulate multiple cancer-related signalling pathways leading to tumour progression and metastasis. Recently, MTA1 was also implicated in cancer metabolism, where it was found to regulate the 'Warburg effect' to drive breast cancer cell invasion. Overall, the functional dynamism of MTA1 can be attributed to its dual co-regulatory effects in regulating a diverse array of target genes involved in cell proliferation, DNA damage repair, angiogenesis, invasion, migration, metastasis, and metabolism in different types of cancers. In this review, we have attempted to provide a brief summary of MTA1 as a modulator of the hallmarks of cancer. [ABSTRACT FROM AUTHOR]

المؤلفون: Da-Qiang Li¹, Reddy, Sirigiri Divijendra Natha¹, Pakala, Suresh B.¹, Xifeng Wu², Yanping Zhang³, Rayala, Suresh K.¹, Kumar, Rakesh¹ bcmrxk@gwumc.edu

المصدر: Journal of Biological Chemistry. 12/11/2009, Vol. 284 Issue 50, p34545-34552. 8p.

مصطلحات موضوعية: *P53 protein, *DNA damage, *DOUBLE-stranded RNA, *NUCLEOTIDES, *DNA repair, *CANCER cells

مستخلص: Although metastasis-associated protein 1 (MTA1) has recently been shown as a DNA damage responsive protein, the underlying mechanism for its role in DNA double-strand break (DSB) repair remains unknown. Here, we show that MTA1 controls p53 stability through inhibiting its ubiquitination by E3 ubiquitin ligases mouse double minute 2 (Mdm2) and constitutive photomorphogenic protein 1 (COP1). The underlying mechanisms involve the ability ofMTA1 to compete with COP! to bind to p53 and/or to destabilize COP1 and Mdm2. Consequently, MTA1 regulates the p53-dependent transcription of p53R2, a direct p53 target gene for supplying nucleotides to repair damaged DNA. Depletion of MTA1 impairs p53-dependent p53R2 transcription and compromises DNA repair. Interestingly, these events could be reversed by MTA1 reintroduction, indicating that MTA1 interjects into the p53-dependent DNA repair. Given the fact that MTA1 is widely up-regulated in human cancers, these findings in conjunction with our earlier finding of a crucial role ofMTA1 in DSB repair suggest an inherent role of the MTA1-p53-p53R2 pathway in DNA damage response in cancer cells. [ABSTRACT FROM AUTHOR]