Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: current knowledge and perspectives.
This article is about Hsp10 and its intracellular and extracellular forms focusing on the relationship of the latter with Early Pregnancy Factor and on their roles in cancer and immunity. Cellular physiology and survival are finely regulated and depend on the correct functioning of the entire set of proteins. Misfolded or unfolded proteins can cause deleterious effects and even cell death. The chaperonins Hsp10 and Hsp60 act together inside the mitochondria to assist protein folding. Recent studies demonstrated that these proteins have other roles inside and outside the cell, either together or independently of each other. For example, Hsp10 was found increased in the cytosol of different tumors (although in other tumors it was found decreased). Moreover, Hsp10 localizes extracellularly during pregnancy and is often indicated as Early Pregnancy Factor (EPF), which is released during the first stages of gestation and is involved in the establishment of pregnancy. Various reports show that extracellular Hsp10 and EPF modulate certain aspects of the immune response with anti-inflammatory effects in patients with autoimmune conditions improving clinically after treatment with recombinant Hsp10. Moreover, Hsp10 and EPF are involved in embryonic development, acting as a growth factor, and in cell proliferation/differentiation mechanisms. Therefore, it becomes evident that Hsp10 is not only a co-chaperonin, but an active player in its own right in various cellular functions. In this article, we present an overview of various aspects of Hsp10 and EPF as they participate in physiological and pathological processes such as the antitumor response and autoimmune diseases.
Corrao
Simona
S
Dipartimento di Medicina Sperimentale, Università degli Studi di Palermo, Via del Vespro 129, 90127, Palermo, Italy. corraosimona@libero.it
Campanella
Claudia
C
Anzalone
Rita
R
Farina
Felicia
F
Zummo
Giovanni
G
Conway de Macario
Everly
E
Macario
Alberto J L
AJ
Cappello
Francesco
F
La Rocca
Giampiero
G
D001327:Autoimmune Diseases / Q000378:metabolism*; D018835:Chaperonin 10 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D021381:Protein Transport; D013491:Suppressor Factors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018835:Chaperonin 10; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C025124:early pregnancy factor