Calreticulin: one protein, one gene, many functions

Michalak, Marek; Corbett, Elaine F.; Mesaeli, Nasrin; Nakamura, Kimitoshi; Opas, Michał

doi:10.1042/0264-6021:3440281

Cited by 491 publications

(358 citation statements)

References 232 publications

Supporting

Mentioning

345

Contrasting

Unclassified

Order By: Relevance

“…C1q binds to calreticulin (CRT) in AC blebs and opsonizes AC for enhanced phagocytosis through C1q interaction with CD91, which is also known as the 2-macroglobulin receptor or low-density lipoprotein receptor-related protein 1 (LRP-1), on phagocytes (18). CRT is a ubiquitously expressed acidic Ca 2+ -binding protein in the endoplasmic reticulum (ER) (19). Despite the finding of CRT expression within the ER it has also been reported as a receptor for C1q (cC1qR) and the collectins including MBL (20,21).…”

Section: C1q Can Directly Opsonize Ac For Phagocytosismentioning

confidence: 99%

See 1 more Smart Citation

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

et al. 2008

View full text Add to dashboard Cite

A classical function of C1q is to bind immune complexes and initiate complement activation producing membrane lytic complexes, opsonins and anaphylatoxins. This classical pathway of complement activation is also elicited when C1q binds some other ligands. Besides complement activation, C1q also regulates cell differentiation, adhesion, migration, activation and survival. C1q deficiency is associated with autoimmunity as well as increased susceptibility to infections. In this article, we discuss the basic properties of C1q, its expression, and classical and regulatory functions. Cellular & Molecular Immunology. 2008;5(1):9-21.

show abstract

Section: C1q Can Directly Opsonize Ac For Phagocytosismentioning

confidence: 99%

“…CRT was first identified as a receptor for C1q that binds to the collagenous region of C1q (20,21). It is a ubiquitous Ca 2+ -binding protein which is naturally retained in the ER lumen and lacks a transmembrane domain (19). On AC, it is found in blebs (18).…”

Section: Cell-associated C1q Ligands or Receptorsmentioning

confidence: 99%

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The generation of pcDNA3-CRT has also been described previously [5]. There is more than 90% homology between rabbit, human, mouse, and rat CRT [26]. For the generation of pcDNA3-NCRT, DNA encoding the N domain of CRT, NCRT was first amplified with PCR by using rabbit CRT cDNA as the template [27] and a set of primers, 5′-CCGG-TCTAGAATGCTGCTCCCTGTGCCGCT-3′ and 5′-CCC-GAATTCGTTGTCCGGCCGCACGATCA-3′.…”

Section: Plasmid Dna Constructs and Preparationmentioning

confidence: 99%

Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

Cheng

Hung

Chen

et al. 2005

Vaccine

View full text Add to dashboard Cite

Antigen-specific cancer immunotherapy and antiangiogenesis are feasible strategies for cancer therapy because they can potentially treat systemic tumors at multiple sites in the body while discriminating between neoplastic and non-neoplastic cells. We have previously developed a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus-16 E7 and have found that this vaccine generates strong E7-specific antitumor immunity and antiangiogenic effects in vaccinated mice. In this study, we characterized the domains of CRT to produce E7-specific antitumor immunity and antiangiogenic effects by generating DNA vaccines encoding each of the three domains of CRT (N, P, and C domains) linked to the HPV-16 E7 antigen. We found that C57BL/6 mice vaccinated intradermally with DNA encoding the N domain of CRT (NCRT), the P domain of CRT (PCRT), or the C domain of CRT (CCRT) linked with E7 exhibited significant increases in E7-specific CD8 + T cell precursors and impressive antitumor effects against E7-expressing tumors compared to mice vaccinated with wild-type E7 DNA. In addition, the N domain of CRT also showed antiangiogenic properties that might have contributed to the antitumor effect of NCRT/E7. Thus, the N domain of CRT can be linked to a tumor antigen in a DNA vaccine to generate both antigen-specific immunity and antiangiogenic effects for cancer therapy.

show abstract

“…Its basic function is to have a critical role in quality control processes during protein synthesis and folding, through binding to misfolded proteins (Tatu and Helenius, 1997). CRT has also been implicated in a variety of functions outside of the endoplasmic reticulum, including cell adhesion, integrindependent Ca 2 þ signaling and expression of steroidsensitive genes (Michalak et al, 1999). CRT enhances cell migration and wound healing (Gold et al, 2006), and influences apoptosis positively or negatively via modulation of intracellular calcium stores (Mesaeli and Phillipson, 2004;Vanoverberghe et al, 2004;Chen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3–CTTN–Akt pathway in esophageal squamous cell carcinoma

Yang

et al. 2009

Oncogene

View full text Add to dashboard Cite

We have shown earlier that overexpression of Calreticulin (CRT) contributed to a poor prognosis for patients with esophageal squamous cell carcinoma (ESCC). Here, we have shown an important role of CRT in tumorigenesis through enhancing cell motility and anoikis resistance. SiRNA-mediated knockdown of CRT caused impaired cell migration, invasion and resistance to anoikis. Notably, CRT downregulation decreased the expression of Cortactin (CTTN), which has been previously reported as a candidate oncogene associated with anoikis through the PI3K-Akt pathway. In addition, Akt phosphorylation was abolished after CRT downregulation and its activation can be refreshed by CRT upregulation, suggesting that CRT-enhanced cell resistance to anoikis through the CRT-CTTN-PI3K-Akt pathway. Moreover, the CTTN mRNA level was decreased in CRT-siRNA cells, coupled with the inactivation of STAT3. Expression of both CTTN and p-STAT3 was reduced in tumor cells following incubation with the JAK-specific inhibitor, AG490. Chromatin immunoprecipitation assay showed direct binding of p-STAT3 to the conservative STAT3-binding sequences in CTTN promoter. Furthermore, overexpression of CTTN in CRT-downregulated ESCC cells restored its motility and resistance to anoikis. This study not only reveals a role of CRT in motility promotion and anoikis resistance in ESCC cells, but also identifies CRT as an upstream regulator in the CRT-STAT3-CTTNAkt pathway.

show abstract

Calreticulin: one protein, one gene, many functions

Cited by 491 publications

References 232 publications

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

The Classical and Regulatory Functions of C1q in Immunity and Autoimmunity

Characterization of DNA vaccines encoding the domains of calreticulin for their ability to elicit tumor-specific immunity and antiangiogenesis

Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3–CTTN–Akt pathway in esophageal squamous cell carcinoma

Contact Info

Product

Resources

About