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Subcellular distribution of calpain-1 and calpain-2 as a key event for calpain-mediated functions in physiological and neoplastic mammary models

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Subcellular distribution of calpain-1 and calpain-2 as a key event for calpain-mediated functions in physiological and neoplastic mammary models

dc.contributor.advisor	Viña Ribes, Juan
dc.contributor.advisor	Ruiz García-Trevijano, Elena
dc.contributor.advisor	Zaragozá Colom, Rosa
dc.contributor.author	Rodríguez Fernández, Lucía
dc.contributor.other	Departament de Bioquímica i Biologia Molecular	es_ES
dc.date.accessioned	2019-04-04T12:17:08Z
dc.date.available	2019-04-05T04:45:05Z
dc.date.issued	2019	es_ES
dc.date.submitted	29-03-2019	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/69799
dc.description.abstract	Calpains are a family of calcium-dependent proteases, which modulate their substrates rather than degrade them in such a way that modifies them. Calpains deregulations have been determined as an aggravating factor of different diseases, including cancer. Nevertheless, there are no clear records about the particular contribution of each calpain isoform in physiological processes and how these isoforms are deregulated in pathological conditions. In vivo, each calpain isoform recognizes specific proteins as substrates, and it has been suggested that calpains subcellular localization might determine their substrate recognition, and consequently their functions. In the present study we have explored the relationship between calpain-1 and calpain-2 isoforms subcellular localization with their involvement in different cell functions, such as cell adhesions cleavage and cell differentiation. Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. To evaluate the isoform-specific CAPN involved in the cleavage of adhesion complexes we used murine mammary gland during involution and breast cancer cell lines as physiological and pathological study models, respectively. We observed a switch in the calpain isoform responsible of this cleavage depending on the biological context: during mammary gland involution, calpain-2 was the isoform ruling this function, while in breast cancer cell lines was calpain-1. In addition, during the second phase of murine mammary gland involution, calpain-1 was gathered in the nuclear compartment of differentiating adipocytes. The relationship between localization and isoform-specific functions of each calpain isoform were explored in the differentiation model of 3T2-L1 cell line. Both isoforms showed a dynamic expression and localization changes along the differentiation course from pre-adipocytes to adipocytes, changes that determined their functions in the differentiation process.	es_ES
dc.format.extent	238 p.	es_ES
dc.language.iso	en	es_ES
dc.subject	calpain-1	es_ES
dc.subject	calpain-2	es_ES
dc.subject	mammary gland involution	es_ES
dc.subject	breast cancer	es_ES
dc.subject	calpain subcellular localization	es_ES
dc.title	Subcellular distribution of calpain-1 and calpain-2 as a key event for calpain-mediated functions in physiological and neoplastic mammary models	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::CIENCIAS DE LA VIDA::Biología celular	es_ES
dc.subject.unesco	UNESCO::CIENCIAS MÉDICAS	es_ES
dc.subject.unesco	UNESCO::CIENCIAS TECNOLÓGICAS::Tecnología bioquímica	es_ES
dc.embargo.terms	0 days	es_ES