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Mitosis and Cancer Biology

Leader:

Hassan Bousbaa

Major interests

More than 80 kinetochore proteins were described that are required for many aspects of kinetcohore function such as kinetochore specification and assembly, microtubule binding, microtubule attachment and dynamic, monitoring; and regulating kinetochore–microtubule attachments to ensure accurate chromosome segregation.

We are using a combination of molecular biology techniques, proteomic based approach, RNAi-mediated gene silencing together with advanced light microscopy in order:
1. to dissect the functions of kinetochore proteins in chromosome segregation and genomic stability, and
2. to the study the relationship of these functions to cancer.
Studies of the kinetochore are relevant to cancer aetiology and treatment. As the kinetochore is required specifically in actively dividing cells, it represents an attractive target for anti-mitotic chemotherapy.

Research Team

Researcher	Position	Email contact
Hassan Bousbaa, PhD	Associate Professor	hassan.bousbaa@iscsn.cespu.pt
Carla Batista Pinto, PhD	Assistant Professor	carlam.pinto@iscsn.cespu.pt
Madalena Pedro, PhD	Assistant Professor	madalena.pedro@iscsn.cespu.pt
Rita Reis, PhD	Research Technician	rita.reis@cespu.pt
Patrícia Silva	Master Student and Research Technician	patricia.silva@ipsn.cespu.pt
Vanessa Nascimento, MSc	PhD Student	ana.nascimento@iscsn.cespu.pt
Joana Barbosa, MSc	Invited Assistant	joana.barbosa@iscsn.cespu.pt
Juliana Faria, MSc	Invited Assistant	juliana.faria@iscsn.cespu.pt
Íris Ferreira	Master Student
Inês Moura	Master Student
Susana Silva	Master Student
Nuno Manuel Martins	Undergraduate Student
Sandra Marques	Undergraduate Student
Vanessa Campos	Undergraduate Student

 

Relevant Publications

Logarinho E and Bousbaa H (2008). Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling. Cell Cycle 7(12):1763-1768.
 
Logarinho E, Resende T, Torres C, and Bousbaa H (2008). The human spindle checkpoint protein Bub3 is required for the establishment of efficient kinetochore-microtubule attachments. Mol Biol Cell 19 (4):1798-1813.
 
Marinho J, Pedro M, Pinto DC, Silva AM, Cavaleiro JA, Sunkel CE, Nascimento MS (2008). 4'-Methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent. Biochem Pharmacol 75(4):826-835.
 
Orr B, Bousbaa H and Sunkel CE (2007). The spindle assembly checkpoint protein Mad2 is only required to prevent premature exit from mitosis. Mol Biol Cell 18:850-863.
 
Benites J, Valderrama JA, Rivera F, Rojo L, Campos N, Pedro M, Nascimento MSJ (2008). Studies on quinones. Part 42: Synthesis of furylquinone and hydroquinones with antiproliferative activity against human tumor cell lines. Bioorg Med Chem 16(2):862-868.
 
Oliveira AM, Raposo MM, Oliveira-Campos AM, Machado AE, Puapairoj P, Pedro M, Nascimento MSJ, Portela C, Afonso C, Pinto M (2006). Psoralen analogues: synthesis, inhibitory activity of growth of human tumor cell lines and computational studies. Eur J Med Chem 41(3): 367-372.
 
Pedro M, Lourenco CF, Cidade H, Kijjoa A, Pinto M, Nascimento MS (2006). Effects of natural prenylated flavones in the phenotypical ER (+) MCF-7 and ER (-) MDA-MB-231 human breast cancer cells. Toxicol Lett 164(1): 24-36.
 
Pedro M, Ferreira MM, Cidade H, Kijjoa A, Bronze-da-Rocha E, Nascimento MS (2005). Artelastin is a cytotoxic prenylated flavone that disturbs microtubules and interferes with DNA replication in MCF-7 human breast cancer cells. Life Sci 77(3): 293-311.
 
Pérez-Mongiovi D, Malmanche N, Bousbaa H, Sunkel CE (2005). Maternal expression of the spindle checkpoint BubR1 is required for synchrony of nuclear syncytial cycles and polar body arrest in Drosophila melanogaster. Development 132:4509-4520 (Cover of the periodical).
 
Logarinho* E, Bousbaa* H, Dias JM, Lopes C, Amorim I, Martins A, Sunkel CE (2004). Different spindle checkpoint proteins monitor microtubule attachment and tension at kinetochores in Drosophila cell. J Cell Sci 117:1757-71 (*The authors contributed equally to this work) (Cover of the periodical).
 
Moiteiro C, Manta C, Justino F, Tavares R, Curto MJ, Pedro M, Nascimento MSJ, Pinto M (2004). Hemisynthetic secofriedelane triterpenes with inhibitory activity against the growth of human tumor cell lines in vitro. J Nat Prod 67(7): 1193-1196.
 
Basu J, Bousbaa H, Logarinho E, Li ZL, Williams BC, Lopes C, Sunkel CE, and Goldberg ML. Mutations in the essential spindle checkpoint gene bub1 cause chromosome missegregation and fail to block apoptosis in Drosophila. J Cell Biol 146:13-28, 1999.
 
Basu J, Logarinho E, Harrmann S, Bousbaa H, Li ZL, Chan GKT, Yen TJ, Sunkel CE, and Goldberg ML. Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not ZW10 or Rod. Chromosoma 107:376-385, 1998.
 
Bousbaa H, Correia L, Gorbsky GJ, and Sunkel CE. Kinetochore phosphoepitopes are expressed in Kc cells, neuroblasts and isolated chromosomes of Drosophila melanogaster. J Cell Sci 110:1979-1988, 1997.

Projects

Project title: Molecular and nanotechnology-based approaches to improve the antitumor activity of small molecules.
Funding Entity: FCT
Project identification: PTDC/SAU-FCF/100930/2008
Period covered: from 01-09-2009 to 01-09-2012
(Project member)
 
Project title: Implementation of the LAP-tagging approach in the Molecular and Cellular Biology Group.
Funding Entity: CESPU, crl
Project identification: 05/GBMC/CICS/2010
Period covered: from 01-01-2010 to 31-12-2011 
 
Project title: Expression profile of mitotic checkpoint genes in a panel of tumor cell lines.
Funding Entity: CESPU, crl
Project identification: 04/GBMC/CICS/09
Period covered: from 01-01-2009 to 31-12-2009
 

Project title: Molecular alterations in the mitotic checkpoint genes in brain cancer cells: hyperphosphorylation
or overexpression?.
Funding Entity: CESPU, crl
Project identification: AL/2007/CESPU
Period covered: from 01-04-2008 to 31-12-2008
 
Project title: Expression of Mitotic Checkpoint Proteins in Human Embryonic Stem Cell Lines: An Immunocytochemical Analysis.
Funding Entity: CESPU, crl
Project identification: AL/2007/CESPU
Period covered: from 01-04-2008 to 31-12-2008
 
Project title: Analyzing the competence of the mitotic checkpoint in brain cancer cell lines.
Funding Entity: CESPU, crl
Project identification: 2F/07/2006/CESPU
Period covered: from 01-04-2006 to 30-09-2007
 
Project title: Analysis of mitotic checkpoint molecular alterations in human brain cancer cell lines.
Funding Entity: CESPU, crl
Project identification: 2F/04/2006/CESPU
Period covered: from 01-04-2006 to 30-09-2007
 
Project title: Linking defective mitotic spindle checkpoint to aneuploidy in brain cancer.
Funding Entity: CESPU, crl
Project identification: AL/07/2006/CESPU
Period covered: from 01-10-2006 to 30-09-2007
 
Project title: Analysis of mitotic spindle checkpoint molecular alterations in human brain cancer cell lines.
Funding Entity: CESPU, crl
Project identification: AL/08/2006/CESPU