57 documents found, page 1 of 6
The role of UPF1 cap-independent translation in colorectal cancer
Lacerda, Rafaela; Menezes,Juliane; Elias, Adriana; Sousa, Sofia de; Romão, LuísaColorectal cancer (CRC) is one of the deadliest diseases worldwide with projections pointing towards an increase for the next two decades. Translation dysregulation of many genes contributes to CRC development, and here we are studying the role of translation dysregulation of up-frameshift 1 (UPF1) in CRC. This protein is involved in many cellular mechanisms such as nonsense-mediated mRNA decay, cell cycle prog...
DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells vi...
García-Moreno, Juan F.; Lacerda, Rafaela; da Costa, Paulo J.; Pereira, Marcelo; Gama-Carvalho, Margarida; Matos, Paulo; Romão, LuísaDIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3’end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is so...
Non-canonical synthesis of UPF1 protein contributes to its oncogenic role in co...
Lacerda, Rafaela; Menezes, Juliane; Antunes Elias, Adriana; Romão, LuísaColorectal cancer (CRC) is the third leading cause worldwide and projections point towards an increase over the next two decades. Gene expression dysregulation of several genes involved in CRC contribute to disease development. The up-frameshift 1 (UPF1) protein plays important roles in several cellular mechanisms and acts as a tumour suppressor in most cancers. However, in CRC, this protein has been described ...
Internal ribosome entry site-mediated translation of UPF1 contributes to its on...
Lacerda, Rafaela; Menezes, Juliane; Elias, Adriana; Romão, LuísaColorectal cancer (CRC) is the third cause of death worldwide and projections point towards an increase for the next two decades. Many genes are misregulated in CRC, contributing to the development of the disease. Up-frameshift 1 (UPF1) is involved in many cellular mechanisms such as nonsense-mediated mRNA decay, cell cycle progression, or telomere maintenance and homeostasis. It also works as a tumour suppress...
The p53 short isoforms are activated by the integrated stress response to enhan...
Ramalho, Ana Catarina; López-Iniesta, Maria José; Lacerda, Rafaela; Parker, Shrutee N.; Romão, Luísa; Candeias, Marco M.Introduction: The full-length p53 (FLp53) protein is a transcriptional factor that mediates cellular stress responses. The appropriate response is modulated according to the nature and extent of the damage, which means that p53 may promote cell cycle arrest and DNA repair or apoptosis in different situations. In all cases, p53 manages the response by modulating the expression of a wide range of target genes, as...
The integrated stress response releases the oncoprotein in TP53
Ramalho, Ana Catarina; López-Iniesta, Maria José; Lacerda, Rafaela; Parker, Shrutee N.; Romão, Luísa; Candeias, Marco M.Introduction: The TP53 gene is surrounded by a great duality: it is a critical tumour suppressor gene, however, its protective nature is frequently lost in tumours, where it becomes a powerful oncogene. Numerous studies attribute the oncogenic profile of TP53 to the missense mutations that commonly occur in cancer. We propose that this duality is intrinsic to TP53 instead of a consequence of mere somatic mutati...
Translational Control of Δ160p53 Keeps the Dark Side of TP53 in Check
Ramalho, Ana Catarina; Lacerda, Rafaela; Romão, Luísa; Candeias, Marco M.The TP53 tumour suppressor gene was discovered over 40 years ago, but to this day some aspects of its regulation and function remain a mystery. It encodes the full-length p53 protein (FLp53), a transcription factor with a key role in stress response in multicellular organisms, that can either direct cells towards apoptosis or recovery of homeostasis. With such a decisive role, its expression and activity are ti...
A iniciação não-canónica da síntese da proteína UPF1 contribui para a sua funçã...
Lacerda, Rafaela; Menezes, Juliane; Antunes Elias, Adriana; Romão, LuísaO cancro colo-rectal (CCR) é a terceira causa de morte ao nível mundial e as projecções apontam para um aumento durante as próximas duas décadas. A desregulação da expressão de vários genes no CCR contribui para o desenvolvimento da doença. A proteína up-frameshift 1 (UPF1) está envolvida em vários mecanismos celulares e, ao contrário da maioria dos cancros, em que a UPF1 desempenha um papel suppressor de tumor...
Conserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isofo...
López-Iniesta, Maria José; Parker, Shrutee; Ramalho, Ana Catarina; Lacerda, Rafaela; Costa, Inês; Zhao, Jingyuan; Romão, Luísa; Candeias, Marcop53 is the most commonly mutated gene in human cancers. Two fundamental reasons for this are its long protein isoforms protect from cancer, while its shorter C-terminal isoforms can support cancer and metastasis. Previously, we have shown that the Δ160p53 protein isoform enhances survival and the invasive character of cancer cells. Here, we identified a translation initiation site nine codons downstream of codo...
Internal Ribosome Entry Site (IRES)-Mediated Translation and Its Potential for ...
Marques, Rita; Lacerda, Rafaela; Romão, LuísaMany conditions can benefit from RNA-based therapies, namely, those targeting internal ribosome entry sites (IRESs) and their regulatory proteins, the IRES trans-acting factors (ITAFs). IRES-mediated translation is an alternative mechanism of translation initiation, known for maintaining protein synthesis when canonical translation is impaired. During a stress response, it contributes to cell reprogramming and ...