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Atlas Genet Cytogenet Oncol Haematol. 2015; 19(9) 575

Atlas of Genetics and Cytogenetics in Oncology and Haematology

INIST-CNRS OPEN ACCESS JOURNAL

HSPD1 (Heat Shock 60kDa Protein 1) Cappello Francesco, Conway de Macario Everly, Macario Alberto JL

Department of Experimental Biomedicine, Clinical Neuroscience, Section of Human Anatomy,

University of Palermo, Palermo, Italy;, Euro-Mediterranean Institute of Science, Technology,

Palermo, Italy (FC); Department of Microbiology, Immunology, School of Medicine, University of

Maryland at Baltimore; Institute of Marine, Environmental Technology (IMET); Columbus Center,

Baltimore, MD 21202, USA (ECdeM); Department of Microbiology, Immunology, School of

Medicine, University of Maryland at Baltimore,, Institute of Marine, Environmental Technology

(IMET), Columbus Center, Baltimore, MD 21202, USA;, Euro-Mediterranean Institute of Science,

Technology, Palermo, Italy (AJLM)

Published in Atlas Database: October 2014

Online updated version : http://AtlasGeneticsOncology.org/Genes/HSPD1ID40888ch2q33.html

Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/62324/10-2014-HSPD1ID40888ch2q33.pdf DOI: 10.4267/2042/62324

This article is an update of : HSPD1 (Heat Shock 60kDa Protein 1). Atlas Genet Cytogenet Oncol Haematol 2015;19(9) Faried A, Faried LS. HSPD1 (Heat Shock 60kDa Protein 1). Atlas Genet Cytogenet Oncol Haematol 2007;11(3)

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2015 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Abstract The HSPD1 gene encodes a protein known as HSP60

or Hsp60, also commonly referred to as Cpn60. This

protein is a molecular chaperone typically localized

inside mitochondria where it forms a chaperoning

machine with HSP10 (encoded by the HSPE1 gene),

also called Cpn10, to assist protein folding inside the

organelle. Hsp60 also occurs in the cytosol, plasma-

cell membrane, intercellular space, and blood. Its

functions in all these extramitochondrial locations

are poorly understood. While the canonical functions

of Hsp60 are considered to be cytoprotective, anti-

stress and maintenance of protein homeostasis, other

roles are currently being investigated. For example,

Hsp60 participates in the pathogenesis of diseases in

various ways in certain types of cancer, and chronic

inflammatory and autoimmune pathological

conditions. These are considered chaperonopathies

by mistake, in which a normal chaperone (normal at

least as far as it can be determined by current

methods to study the structure of a molecule

available only at extremely low concentrations and

quantities) turns against the organism instead of

protecting it, favouring the growth and

dissemination of cancer cells, or the initiation-

progression of inflammation, for instance. In

addition, Hsp60 mutations cause at least two types of

severe genetic chaperonopathies. All this knowledge

is expanding nowadays clearly pointing to Hsp60 as

a potential target for chaperonotherapy by

replacement when it is defective or by inhibition

when it is pathogenic.

Keywords

HSPD1, HSP60, Cpn60, GroEL, chaperonin,

chaperone, protein folding, mitochondria,

extramitochondrial sites, cancer, chronic

inflammatory conditions, autoimmune diseases,

chaperonopathies by mistake, chaperonotherapy

Identity

Other names: HSP60, HSP65, HuCHA60,

Chaperonin 60kDa (CPN60), GROEL, SPG13

HGNC (Hugo): HSPD1

Location: 2q33.1

HSPD1 (Heat Shock 60kDa Protein 1) Cappello F, et al.


Hsp60 and Hsp10 protein/gene/genomic data.

The molecular anatomy of the human Hsp60: structural domains. Left: The anatomy of the human Hsp60: structural domains. The cartoon represents a three-dimensional model of the human Hsp60 monomer showing its three structural domains:

apical in green, intermediate in yellow and equatorial in red. Right: This picture presents the ATP and Mg+/K+ binding sites on Hsp60. Particularly it shows two highly conserved sequences: 52-DGVTVAKEI-60 (orange-brown), and 85-AGDGTTTATVL-95 (magenta) corresponding to the binding sites for Mg+/K+ (green and yellow spheres, respectively) and ATP/ADP (red). Source:

Cappello et al., Expert Opin Ther Targets. 2014 ; 18 (2) : 185-208. PMID 24286280.



DNA/RNA

Description

The human HSP60 gene (HSPD1) contains 12 exons

and 11 introns and was predicted to span over

approximately 13 kb of the genomic DNA. The first

exon is non-coding region (Hansen et al., 2003;

Mukherjee et al., 2010).

Transcription

Two transcript variants encoding the same protein

have been identified for HSPD1

http://www.ncbi.nlm.nih.gov/gene/3329; Mukherjee

et al., 2010).

Pseudogene

Twelve pseudogenes located on chromosome 3, 4, 5,

6, 8 and 12 have been associated with HSP60

(Mukherjee et al., 2010).

Protein

Description

The HSP60 consists of 573 amino acids

corresponding to a molecular weight of 61.05 kDa

(Mukherjee et al., 2010). The HSP60 protein are

abundant proteins of eubacteria genomes and

mitochondria in eukaryotes, and also occurs in other

locations, such as the cellular cytosol, plasma-cell

membrane, and extracellular space (including blood)

in eukaryotic organisms.

HSP60 belongs to the chaperone subgroup called

chaperonins, of which two varieties are known:

chaperonins of Group I and chaperonins of Group II.

The former include the human HSP60 typically

present in the mitochondria (but also occurring in

other locations as described above) and the bacterial

GroEL. Chaperonins of Group II include the

archaeal thermosome subunits and the cytosolic

chaperonin CCT (Chaperonin-containing TCP-1).

The human HSP60 and the bacterial GroEL form

oligomers: seven monomers associate to form a ring

and two rings associate end to end to build a large

chaperoning machine of fourteen subunits, all

identical. This tetradecamer is the HSP60 functional

chaperoning complex that associates with Hsp60 and

requires ATP and ATPase activity for the folding of

substrates (Cappello et al., 2014).

Expression

HSP60 expression is virtually ubiquitous, since it

can be found in cells of different tissues and organs,

including immune system, epithelial tissue and other

cells (Cappello et al., 2011a). However, sometimes

its levels can be under the threshold of

detectability by immunomorphology or

immunoblotting.

It can also be found in the blood (Shamaei-Tousi et

al., 2007).

Localisation

HSP60 subcellular localization is mainly in the

mitochondria, but it also occurs in extra-

mitochondrial sites such as the cytosol, cell surface,

peroxisomes, and the endoplasmic reticulum (Soltys

and Gupta, 1996; Soltys and Gupta, 1999; Gupta et

al., 2008).

Levels of extramitochondrial localization increase

during inflammatory states (Rodolico et al., 2010;

Tomasello et al., 2011; Cappello et al., 2011b) and

tumorigenesis (Cappello et al., 2008; Cappello et al.,

2011c; Campanella et al., 2012; Rappa et al., 2012).

Function

Assisting mitochondrial protein folding, unfolding,

and degradation (Bukau and Horwich, 1998; Fink,

1999; Slavotinek and Biesecker, 2001; Thirumalai

and Lorimer, 2001; Corrao et al., 2010).

HSP60 also have anti-apoptosis and pro-apoptosis

roles in different pathophysiologic conditions such

as heart failure (Knowlton et al., 1998; Kirchhoff et

al., 2002; Gupta and Knowlton, 2005; Lin et al,

2007; Kim et al., 2009) and cancer (Chandra et al.,

2007; Campanella et al., 2008).

Homology

Up to now more than 150 homologues of HSP60

sequences with pair-wise similarity extending from

40-100% at the amino acid level. Among these

homologues one can mention those from rat rat

(Rattus norvegicus), pufferfish (Fugu rubripes),

zebrafish (Danio rerio), the nematode

Caenorhabditis elegans, mouse (Mus musculus), and

Chlamydia trachomatis (Gupta, 1995). Moreover,

Hsp60 presents a high structural homology with

other human proteins, that may act as autoantigen,

such as acetylcholine receptor, thyroglobulin, etc.

(Jones et al., 1993).

The high homology between Hsp60 of several

bacterial species and the human protein led to

postulate its involvement in molecular mimicry

phenomena with pathogenic implications

(Campanella et al., 2009; Cappello et al., 2009).

Moreover, the high homology between human and

bacterial Hsp60 and other human autoantigens led to

postulate its role in the autoimmune manifestations

of some autoimmune diseases, such as myasthenia

gravis (Cappello et al., 2010; Marino Gammazza et

al., 2012) and Hashimoto's thyroiditis (Marino

Gammazza et al., 2014).



The human hsp60 genes and pseudogenes: genomic data. Source: Mukherjee et al. BMC Evolutionary Biology 2010 10:64. PMID 20193073



Hsp60 presence and localization in normal tissues. Top: Normal human bronchial mucosa. Ciliated cells present Hsp60 positivity by immunohistochemistry (IHC) in the cytosol (red spots, see arrow for example). Bottom: Normal human colonic

mucosa. Intestinal cells do not show any positivity for Hsp60 at IHC, since the protein is under the threshold of detectability. Modified from: Cappello et al., Methods Mol Biol. 2011 ; 787 : 245-254. PMID 21898240



Hsp60 localization localization in pathologic tissues. Top: Epithelial cell of inflamed colonic mucosa (patient with ulcerative colitis) showing Hsp60 positivity (immunogold) in cytosol (arrows). Modfied from Tomasello et al., 2011). Bottom: Pulmonary mucoepidermoid carcinoma cell (H292) showing Hsp60 positivity (immunogold) in cytosol and at plasma-cell membrane level

(arrows). Inset: a classical mitochondrial positivity for Hsp60.Modified from Campanella et al., PLoS One. 2012 ; 7 (7) : e42008. PMID 22848686



Hsp60 function. Hsp60 works in cooperation with Hsp10, its co-chaperonin, to assist protein folding of unfolded mitochondrial proteins by an ATP dependent mechanism. Modified from www.pdbj.org.

http://www.pdbj.org/



Mutations

Germinal Not known in Homo sapiens.

Somatic Hereditary spastic paraplegia (SPG13) is associated

with a mutation in the HSP60 gene: the amino acid

72 Valine is changed to Isoleucine (Hansen et al.,

2002).

MitCHAP-60 disease is associated with a mutation

in the HSP60 gene: The amino acid 29 Aspartic acid

is changed to Glycine (Magen et al., 2008).

General note: HSP60 expression (mRNA) and levels (protein)

were elevated, decreased or without changes in a

number of cancers studied by independent groups

with various techniques.

For a review on this topic see: Czarnecka et al., 2006;

Cappello et al., 2008; Rappa et al., 2012; Macario et

al., 2013).

Moreover, cancer cells, but not the normal

counterparts release HSP60 via exosomes

(Merendino et al., 2010; Campanella et al., 2012).

Further studies on this topic are currently under way

to better understand why Hsp60 levels change during

carcinogenesis and what is the role of this protein in

cancer progression

Epigenetics Not known in Homo sapiens.

Implicated in

Autoimmune diseases

Note

First clinical trials using HSP60 (peptide 277) has

been tested in type-2 diabetes.

Disease

HSP60 has been implicated in T cell activation and

cause inflammatory reaction. It has been involved in

the pathogenesis of a number of autoimmune

diseases and inflammatory conditions such as type-1

diabetes, juvenile chronic arthritis, atherosclerosis,

Crohn disease, rheumatoid arthritis, systemic lupus

erythematosus, Sjogren syndrome, Hashimoto

thyroiditis, and myasthenia gravis (Campanella et

al., 2009; Cappello et al., 2009; Cappello et al., 2010;

Marino Gammazza et al., 2012; Marino Gammazza

et al., 2014).

Colon cancer

Note

For a review on Hsp60 in colon cancer, see Cappello

et al., 2011c.

Disease

Hsp60 expression and levels were increased in colon

cancer of various grades and stages compared to

controls (Cappello et al., 2005a). This has been

confirmed by other independent groups (Mori et al.,

2005; He et al., 2007).



Prognosis

Hsp60 has been described as a potential serum

marker for colorectal cancer (Hamelin et al., 2011).

Oncogenesis

Hsp60 levels increase gradually through the

carcinogenic steps (i.e., normal-to-dysplasia-to-

carcinoma sequence) and Hsp60 is a good marker to

distinguish dysplastic from normal cells (Cappello et

al., 2003a).

Lung cancer.

Note

The four major histological types of carcinoma of the

lung are: squamous cell carcinoma (SCC),

adenocarcinoma (AD), small cell carcinoma

(SCLC), and large cell carcinoma (LCC). In some

cases there can be a combination of histological

patterns (Husain and Kumar, 2005).

Disease

Hsp60 levels were decreased in adenocarcinoma and

adenosquamous carcinoma compared to controls

(Cappello et al., 2005b; Cappello et al., 2006a).

However, this has not been confirmed by another

independent group (Xu et al., 2011) that in a series

of lung adenocarcinomas found increased levels of

Hsp60 compared to controls. The authors postulated

that the possible reason to explain this contrasting

data may be two: different TNM stages and different

part of the tumor biopsied (e.g., central versus

periphery).

Prognosis

Hsp60 levels were significantly correlated with

TNM stage of the tumor and Eastern Cooperative

Oncology Group performance status (Xu et al.,

2011). Multivariate statistical analysis showed that

patient age, pathological T stage, N stage, and Hsp60

expression were independent prognostic indicators

with regard to disease-free survival (Xu et al., 2011).

Oncogenesis

Hsp60 levels decrease gradually through

carcinogenetic steps of lung (i.e., normal-to-

dysplasia-to-carcinoma sequence) (Cappello et al.,

2005b; Cappello et al., 2006a).

Prostate cancer

Note

Prostate cancer is preceded by the so called 'prostate

intraneoplastic lesion' or PIN, a dysplastic

(pretumoral) lesion.

Prostatic hyperplasia is not considered a

preneoplastic condition (Bostwick and Chen, 2012).

Gleason score is an index of malignancy: the higher

it is, the worse is the prognosis (Egevad et al., 2012).

Prostate specific antigen (PSA) is a serum marker

used for prostate cancer diagnosis and follow-up

(Loeb et al., 2014).

Disease

Many studies have shown that Hsp60 levels are

increased in prostate cancer, using

immunohistochemistry (Cornford et al., 2000;

Cappello et al., 2003b; Johansson et al., 2006), and

proteomics (Skyortsov et al., 2011). HSP60 was

significantly increased in both early and advanced

prostate cancers when compared with non-neoplastic

prostatic epithelium (Cornford et al., 2000). In non-

malignant prostate, HSP60-staining is localized in

the glandular compartment, particularly basal

epithelial cells. In prostate cancer, most epithelial

cells showed moderate to strong staining without

apparent correlation between staining intensity and

Gleason grade (Johansson et al., 2006).

Prognosis

Recurrence-free survival in patients with strong

HSP60 staining was shorter than in those with weak

levels (Glaessgen et al., 2008). In another study, the

levels of HSP60 were significantly increased in

tumors with high Gleason score. HSP60 expression

was also significantly associated with initial serum

PSA levels and with the presence of lymph node

metastasis (Castilla et al., 2010).

Oncogenesis

HSP60 levels increase gradually through

carcinogenic steps (from PIN to carcinoma) of

prostate (Cappello et al., 2003b).

Exocervical cancer

Note

Exocervical cancer is preceded by the so called

'squamous intraepithelial lesion' or SIL, a dysplastic

(pretumoral) lesion (Garrett and McCann, 2013).

SIL, as well as exocervical cancer, have been related

to infection by Human Papilloma Virus (HPV)

(Garrett and McCann, 2013).

Disease

Hsp60 levels are increased in exocervical cancer, as

shown by immunohistochemistry (Cappello et al.,

2002-2003; Castle et al., 2005).

Oncogenesis

HSP60 levels increase gradually through

carcinogenic steps (from SIL to carcinoma) of

exocervix (Cappello et al., 2002-2003).

Vesical cancer

Disease

HSP60 levels are decreased in vesical cancers such

as bladder carcinoma (Lebret et al., 2003; Cappello

et al., 2006b).

Prognosis

HSP60 is considered a useful marker for patients

with superficial bladder carcinoma for predicting

disease progression: lower levels correlate with

worse outcome of local treatments. Particularly,

HSP60 levels are considered useful prognostic

marker to identify patients for whom local treatment



would be insufficient (Lebret et al., 2003). Hsp60

levels may predict response to neoadjuvant

chemoradiotherapy in invasive or high-risk

superficial bladder cancer (Urushibara et al., 2007).

To be noted HSP60 may participate in the process of

carcinogenesis, representing cases of

chaperonopathies by mistake or collaborationism in

which a normal chaperone (at least considering the

methods available nowadays to characterize

intracellular molecules, or extracellular molecules at

very low concentrations) contributes to cancer

development (Macario et al., 2013).

HSP60 may participate also in the process of chronic

inflammation (Cappello et al., 2011b) and

autoimmune diseases (Cappello et al., 2009), also by

molecular mimicry phenomena. For example,

atherosclerosis has been postulated to be an

autoimmune disease due to an immune reaction

against heat-shock protein 60 (Wick et al., 2014).

References Bostwick DG, Cheng L. Precursors of prostate cancer. Histopathology. 2012 Jan;60(1):4-27

Bukau B, Horwich AL. The Hsp70 and Hsp60 chaperone machines. Cell. 1998 Feb 6;92(3):351-66

Campanella C, Bucchieri F, Merendino AM, Fucarino A, Burgio G, Corona DF, Barbieri G, David S, Farina F, Zummo G, de Macario EC, Macario AJ, Cappello F. The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities. PLoS One. 2012;7(7):e42008

Cappello F, Marino Gammazza A, Palumbo Piccionello A, Campanella C, Pace A, Conway de Macario E, Macario AJ. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin Ther Targets. 2014 Feb;18(2):185-208

Castilla C, Congregado B, Conde JM, Medina R, Torrubia FJ, Japón MA, Sáez C. Immunohistochemical expression of Hsp60 correlates with tumor progression and hormone resistance in prostate cancer. Urology. 2010 Oct;76(4):1017.e1-6

Castle PE, Ashfaq R, Ansari F, Muller CY. Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix. Cancer Lett. 2005 Nov 18;229(2):245-52

Cornford PA, Dodson AR, Parsons KF, Desmond AD, Woolfenden A, Fordham M, Neoptolemos JP, Ke Y, Foster CS. Heat shock protein expression independently predicts clinical outcome in prostate cancer. Cancer Res. 2000 Dec 15;60(24):7099-105

Corrao S, Campanella C, Anzalone R, Farina F, Zummo G, Conway de Macario E, Macario AJ, Cappello F, La Rocca G. Human Hsp10 and Early Pregnancy Factor (EPF) andtheir relationship and involvement in cancer and immunity:current knowledge and perspectives. Life Sci. 2010 Jan30;86(5-6):145-52

Czarnecka AM, Campanella C, Zummo G, Cappello F. Mitochondrial chaperones in cancer: from molecular biology

to clinical diagnostics. Cancer Biol Ther. 2006 Jul;5(7):714-20

Egevad L, Mazzucchelli R, Montironi R. Implications of the International Society of Urological Pathology modified Gleason grading system. Arch Pathol Lab Med. 2012 Apr;136(4):426-34

Fink AL. Chaperone-mediated protein folding. Physiol Rev. 1999 Apr;79(2):425-49

Gammazza AM, Bucchieri F, Grimaldi LM, Benigno A, de Macario EC, Macario AJ, Zummo G, Cappello F. The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis. Cell Mol Neurobiol. 2012 Aug;32(6):943-7

Garrett LA, McCann CK. Abnormal cytology in 2012: management of atypical squamous cells, low-grade intraepithelial neoplasia, and high-grade intraepithelial neoplasia. Clin Obstet Gynecol. 2013 Mar;56(1):25-34

Glaessgen A, Jonmarker S, Lindberg A, Nilsson B, Lewensohn R, Ekman P, Valdman A, Egevad L. Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS. 2008 Oct;116(10):888-95

Gupta RS, Ramachandra NB, Bowes T, Singh B. Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10. Novartis Found Symp. 2008;291:59-68; discussion 69-73, 137-40

Gupta S, Knowlton AA. HSP60, Bax, apoptosis and the heart. J Cell Mol Med. 2005 Jan-Mar;9(1):51-8

Hamelin C, Cornut E, Poirier F, Pons S, Beaulieu C, Charrier JP, Haïdous H, Cotte E, Lambert C, Piard F, Ataman-Önal Y, Choquet-Kastylevsky G. Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer. FEBS J. 2011 Dec;278(24):4845-59

Hansen JJ, Bross P, Westergaard M, Nielsen MN, Eiberg H, Børglum AD, Mogensen J, Kristiansen K, Bolund L, Gregersen N. Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter. Hum Genet. 2003 Jan;112(1):71-7

Hansen JJ, Dürr A, Cournu-Rebeix I, Georgopoulos C, Ang D, Nielsen MN, Davoine CS, Brice A, Fontaine B, Gregersen N, Bross P. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet. 2002 May;70(5):1328-32

He Y, Wu Y, Mou Z, Li W, Zou L, Fu T, Zhang A, Xiang D, Xiao H, Wang X. Proteomics-based identification of HSP60 as a tumor-associated antigen in colorectal cancer. Proteomics Clin Appl. 2007 Mar;1(3):336-42

Husain A, Kumar V. The lung. In: Robbins, Cotran. Pathologic Basis of Disease, 7th edn. Philadelphia: Saunders;2005, 711-772.

Johansson B, Pourian MR, Chuan YC, Byman I, Bergh A, Pang ST, Norstedt G, Bergman T, Pousette A. Proteomic comparison of prostate cancer cell lines LNCaP-FGC and LNCaP-r reveals heatshock protein 60 as a marker for prostate malignancy Prostate 2006 Sep 1;66(12):1235-44

Jones DB, Coulson AF, Duff GW. Sequence homologies between hsp60 and autoantigens Immunol Today 1993 Mar;14(3):115-8

Kim SC, Stice JP, Chen L, Jung JS, Gupta S, Wang Y, Baumgarten G, Trial J, Knowlton AA. Extracellular heat



shock protein 60, cardiac myocytes, and apoptosis Circ Res 2009 Dec 4;105(12):1186-95

Kirchhoff SR, Gupta S, Knowlton AA. Cytosolic heat shock protein 60, apoptosis, and myocardial injury Circulation 2002 Jun 18;105(24):2899-904

Knowlton AA, Kapadia S, Torre-Amione G, Durand JB, Bies R, Young J, Mann DL. Differential expression of heat shock proteins in normal and failing human hearts J Mol Cell Cardiol 1998 Apr;30(4):811-8

Lebret T, Watson RW, Molinié V, O'Neill A, Gabriel C, Fitzpatrick JM, Botto H. Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma Cancer 2003 Sep 1;98(5):970-7

Lin L, Kim SC, Wang Y, Gupta S, Davis B, Simon SI, Torre-Amione G, Knowlton AA. HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis Am J Physiol Heart Circ Physiol 2007 Oct;293(4):H2238-47

Loeb S, Bruinsma SM, Nicholson J, Briganti A, Pickles T, Kakehi Y, Carlsson SV, Roobol MJ. Active Surveillance for Prostate Cancer: A Systematic Review of Clinicopathologic Variables and Biomarkers for Risk Stratification Eur Urol 2015 Apr;67(4):619-626

Macario AJL, Conway de Macario AJL, Cappello F. The Chaperonopathies. Diseases with Defective Molecular Chaperones. SpringerBriefs in Biochemistry and Molecular Biology. 2013, XVI, pp 75-79. http://www.springer.com/biomed/book/978-94-007-4666-4

Magen D, Georgopoulos C, Bross P, Ang D, Segev Y, Goldsher D, Nemirovski A, Shahar E, Ravid S, Luder A, Heno B, Gershoni-Baruch R, Skorecki K, Mandel H. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy Am J Hum Genet 2008 Jul;83(1):30-42

Marino Gammazza A, Rizzo M, Citarrella R, Rappa F, Campanella C, Bucchieri F, Patti A, Nikolic D, Cabibi D, Amico G, Conaldi PG, San Biagio PL, Montalto G, Farina F, Zummo G, Conway de Macario E, Macario AJ, Cappello F. Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis Cell Stress Chaperones 2014 May;19(3):343-53

Merendino AM, Bucchieri F, Campanella C, Marcianò V, Ribbene A, David S, Zummo G, Burgio G, Corona DF, Conway de Macario E, Macario AJ, Cappello F. Hsp60 is actively secreted by human tumor cells PLoS One 2010 Feb 16;5(2):e9247

Mori D, Nakafusa Y, Miyazaki K, Tokunaga O. Differential expression of Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2) in human colorectal cancer progression using human cancer cDNA microarrays Pathol Res Pract 2005;201(12):777-89

Mukherjee K, Conway de Macario E, Macario AJ, Brocchieri L. Chaperonin genes on the rise: new divergent classes andintense duplication in human and other vertebrate genomesBMC Evol Biol 2010 Mar 1;10:64

Rappa F, Farina F, Zummo G, David S, Campanella C, Carini F, Tomasello G, Damiani P, Cappello F, DE Macario EC, Macario AJ. HSP-molecular chaperones in cancer biogenesis and tumor therapy: an overview Anticancer Res 2012 Dec;32(12):5139-50

Rodolico V, Tomasello G, Zerilli M, Martorana A, Pitruzzella A, Gammazza AM, David S, Zummo G, Damiani P, Accomando S, Conway de Macario E, Macario AJ, Cappello F. Hsp60 and Hsp10 increase in colon mucosa of Crohnsdisease and ulcerative colitis Cell Stress Chaperones 2010Nov;15(6):877-84

Shamaei-Tousi A, Steptoe A, O'Donnell K, Palmen J, Stephens JW, Hurel SJ, Marmot M, Homer K, D'Aiuto F, Coates AR, Humphries SE, Henderson B. Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors Cell Stress Chaperones 2007 Winter;12(4):384-92

Skvortsov S, Schäfer G, Stasyk T, Fuchsberger C, Bonn GK, Bartsch G, Klocker H, Huber LA. Proteomics profiling of microdissected low- and high-grade prostate tumors identifies Lamin A as a discriminatory biomarker J Proteome Res 2011 Jan 7;10(1):259-68

Slavotinek AM, Biesecker LG. Unfolding the role of chaperones and chaperonins in human disease Trends Genet 2001 Sep;17(9):528-35

Soltys BJ, Gupta RS. Mitochondrial-matrix proteins at unexpected locations: are they exported? Trends Biochem Sci 1999 May;24(5):174-7 Review

Thirumalai D, Lorimer GH. Chaperonin-mediated protein folding Annu Rev Biophys Biomol Struct 2001;30:245-69

Tomasello G, Rodolico V, Zerilli M, Martorana A, Bucchieri F, Pitruzzella A, Marino Gammazza A, David S, Rappa F, Zummo G, Damiani P, Accomando S, Rizzo M, de Macario EC, Macario AJ, Cappello F. Changes in immunohistochemical levels and subcellular localization after therapy and correlation and colocalization with CD68 suggest a pathogenetic role of Hsp60 in ulcerative colitis Appl Immunohistochem Mol Morphol 2011 Dec;19(6):552-61

Urushibara M, Kageyama Y, Akashi T, Otsuka Y, Takizawa T, Koike M, Kihara K. HSP60 may predict good pathological response to neoadjuvant chemoradiotherapy in bladder cancer Jpn J Clin Oncol 2007 Jan;37(1):56-61

Wick G, Jakic B, Buszko M, Wick MC, Grundtman C. The role of heat shock proteins in atherosclerosis Nat Rev Cardiol 2014 Sep;11(9):516-29

Xu X, Wang W, Shao W, Yin W, Chen H, Qiu Y, Mo M, Zhao J, Deng Q, He J. Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma J Surg Oncol 2011 Nov 1;104(6):598-603

This article should be referenced as such:

Cappello F, Conway de Macario E, Macario AJL. HSPD1 (Heat Shock 60kDa Protein 1). Atlas Genet Cytogenet Oncol Haematol. 2015; 19(9):575-585.

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