Raffaele Frazzi1. 1. Laboratory of Translational Research, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Viale Risorgimento 80, Reggio Emilia, Italy. raffaele.frazzi@ausl.re.it.
Abstract
BACKGROUND: The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight members of the human IAPs family. This family is characterized by the presence of the baculoviral IAP repeat (BIR) domains, involved in protein-protein interactions. In addition to the BIR domains, IAPs also contain other important domains like the C-terminal ubiquitin-conjugating (UBC) domain, the caspase recruitment (CARD) domain and the C-terminal Ring zinc-finger (RING) domain. MAIN BODY: BIRC3 and BIRC5 have been characterized in some solid and hematological tumors and are therapeutic targets for the family of drugs called "Smac mimetics". Many evidences point to the pro-survival and antiapoptotic role of BIRC3 in cancer cells, however, not all the data are consistent and the resulting picture is heterogeneous. For instance, BIRC3 genetic inactivation due to deletions or point mutations is consistently associated to shorter progression free survival and poor prognosis in chronic lymphocytic leukemia patients. BIRC3 inactivation has also been associated to chemoimmunotherapy resistance. On the contrary, the progression from low grade gliomas to high grade gliomas is accompanied by BIRC3 expression increase, which bears relevant prognostic consequences. Due to the relationship between BIRC3, MAP3K14 and the non-canonical NF-kB pathway, BIRC3 inactivation bears consequences also on the tumor cells relying on NF-kB pathway to survive. BIRC5, on the contrary, is commonly considered an anti-apoptotic molecule, promoting cell division and tumor progression and it is widely regarded as potential therapeutic target. CONCLUSIONS: The present manuscript collects and reviews the most recent literature concerning the role played by BIRC3 and BIRC5 in cancer cells, providing useful information for the choice of the best therapeutic targets.
BACKGROUND: The evasion from apoptosis is a common strategy adopted by most tumors, and inhibitors of apoptosis proteins (IAPs) are among the most studied molecular and therapeutic targets. BIRC3 (cellular IAP2) and BIRC5 (survivin) are two of the eight members of the human IAPs family. This family is characterized by the presence of the baculoviral IAP repeat (BIR) domains, involved in protein-protein interactions. In addition to the BIR domains, IAPs also contain other important domains like the C-terminal ubiquitin-conjugating (UBC) domain, the caspase recruitment (CARD) domain and the C-terminal Ring zinc-finger (RING) domain. MAIN BODY: BIRC3 and BIRC5 have been characterized in some solid and hematological tumors and are therapeutic targets for the family of drugs called "Smac mimetics". Many evidences point to the pro-survival and antiapoptotic role of BIRC3 in cancer cells, however, not all the data are consistent and the resulting picture is heterogeneous. For instance, BIRC3 genetic inactivation due to deletions or point mutations is consistently associated to shorter progression free survival and poor prognosis in chronic lymphocytic leukemia patients. BIRC3 inactivation has also been associated to chemoimmunotherapy resistance. On the contrary, the progression from low grade gliomas to high grade gliomas is accompanied by BIRC3 expression increase, which bears relevant prognostic consequences. Due to the relationship between BIRC3, MAP3K14 and the non-canonical NF-kB pathway, BIRC3 inactivation bears consequences also on the tumor cells relying on NF-kB pathway to survive. BIRC5, on the contrary, is commonly considered an anti-apoptotic molecule, promoting cell division and tumor progression and it is widely regarded as potential therapeutic target. CONCLUSIONS: The present manuscript collects and reviews the most recent literature concerning the role played by BIRC3 and BIRC5 in cancer cells, providing useful information for the choice of the best therapeutic targets.
Authors: Sara Raponi; Ilaria Del Giudice; Caterina Ilari; Luciana Cafforio; Monica Messina; Luca V Cappelli; Silvia Bonina; Alfonso Piciocchi; Marilisa Marinelli; Nadia Peragine; Paola Mariglia; Francesca R Mauro; Gian M Rigolin; Francesca Rossi; Riccardo Bomben; Michele Dal Bo; Giovanni Del Poeta; Fary Diop; Chiara Favini; Davide Rossi; Gianluca Gaidano; Antonio Cuneo; Valter Gattei; Anna Guarini; Robin Foá Journal: Br J Haematol Date: 2018-05-22 Impact factor: 6.998
Authors: Matthew J J Rose-Zerilli; Jade Forster; Helen Parker; Anton Parker; Ana E Rodríguez; Tracy Chaplin; Anne Gardiner; Andrew J Steele; Andrew Collins; Bryan D Young; Anna Skowronska; Daniel Catovsky; Tatjana Stankovic; David G Oscier; Jonathan C Strefford Journal: Haematologica Date: 2014-02-28 Impact factor: 9.941
Authors: Takeshi Shimamura; Danan Li; Hongbin Ji; Henry J Haringsma; Elizabeth Liniker; Christa L Borgman; April M Lowell; Yuko Minami; Kate McNamara; Samanthi A Perera; Sara Zaghlul; Roman K Thomas; Heidi Greulich; Susumu Kobayashi; Lucian R Chirieac; Robert F Padera; Shigeto Kubo; Masaya Takahashi; Daniel G Tenen; Matthew Meyerson; Kwok-Kin Wong; Geoffrey I Shapiro Journal: Cancer Res Date: 2008-07-15 Impact factor: 12.701
Authors: Enrique González-Madrid; Ma Andreina Rangel-Ramírez; María José Mendoza-León; Oscar Álvarez-Mardones; Pablo A González; Alexis M Kalergis; Ma Cecilia Opazo; Claudia A Riedel Journal: Int J Mol Sci Date: 2022-06-25 Impact factor: 6.208
Authors: Getinet M Adinew; Samia S Messeha; Equar Taka; Ramesh B Badisa; Lovely M Antonie; Karam F A Soliman Journal: Nutrients Date: 2022-05-19 Impact factor: 6.706