COMMD1 (Copper Metabolism MURR1 Domain-containing Protein 1) Regulates Cullin RING Ligases by Preventing CAND1 (Cullin-associated Nedd8-dissociated Protein 1) Binding

Mao, Xiaoyu; Gluck, Nathan; Chen, Baozhi; Starokadomskyy, Petro; Li, Haiying; Maine, Gabriel N.; Burstein, Ezra

doi:10.1074/jbc.m111.278408

Cited by 41 publications

(47 citation statements)

References 40 publications

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“…Moreover, precipitation of endogenous CCDC22 led to the recovery of endogenous Cul1, Cul2, and Cul3 ( Figure 6C). Finally, CCDC22 was able to interact with other Cullin family members (Supplemental Figure 9A), in line with similar observations for COMMD family members (16). Together, these data demonstrated that CCDC22 interacts with the ligase that targets IκB proteins for degradation and is required for its ability to ubiquitinate this substrate in vivo.…”

Section: Figuresupporting

confidence: 72%

“…We postulate that the specific composition of COMMD proteins present in any given CCDC22-COMMD complex, as well as the specific CRLs to which they bind, ultimately determine their unique functions. In addition, we speculate that CCDC22 and COMMD proteins work in concert to regulate these ligases, probably acting as a complex to displace the CRL inhibitor CAND1, as recently reported in the case of COMMD1 (16).…”

Section: Figurementioning

confidence: 83%

“…Our results indicated that CCDC22 promotes IκB ubiquitination and degradation, and we reasoned that this effect might be mediated by CCDC22's interaction with another COMMD family member or might be COMMD independent. To identify a possible COMMD protein that might be similarly involved in the degradation of IκB, we focused our attention on COMMD family members that interact with Cul1 (the central subunit in the CRL1-βTrCP complex), such as COMMD8 and COMMD10 (16). COMMD8 repression led to decreased IκB-α degradation, an effect not seen after COMMD1 or COMMD10 RNAi (Figure 7, A and B).…”

Section: Figurementioning

confidence: 99%

“…All other plasmids used were described previously (1,3,16,25,28,(46)(47)(48). See Supplemental Table 1 for target sequences of the siRNA duplexes used.…”

Section: Figurementioning

confidence: 99%

“…ylation of RelA (24,25) and is mediated by a CRL2 complex that depends on COMMD1 for its activation (12,16). Interestingly, while certain COMMD proteins, such as COMMD8 and COMMD10, bind to Cul1 (16), it was not previously known whether these factors promote the ubiquitination of CRL1 targets such as IκB.…”

mentioning

confidence: 99%

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CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling

Starokadomskyy¹,

Gluck²,

Li³

et al. 2013

J. Clin. Invest.

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NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis of immune disorders and cancer. Its regulation involves a variety of steps, including the controlled degradation of inhibitory IκB proteins. In addition, the inactivation of DNA-bound NF-κB is essential for its regulation. This step requires a factor known as copper metabolism Murr1 domain-containing 1 (COMMD1), the prototype member of a conserved gene family. While COMMD proteins have been linked to the ubiquitination pathway, little else is known about other family members. Here we demonstrate that all COMMD proteins bind to CCDC22, a factor recently implicated in X-linked intellectual disability (XLID). We showed that an XLID-associated CCDC22 mutation decreased CCDC22 protein expression and impaired its binding to COMMD proteins. Moreover, some affected individuals displayed ectodermal dysplasia, a congenital condition that can result from developmental NF-κB blockade. Indeed, patient-derived cells demonstrated impaired NF-κB activation due to decreased IκB ubiquitination and degradation. In addition, we found that COMMD8 acted in conjunction with CCDC22 to direct the degradation of IκB proteins. Taken together, our results indicate that CCDC22 participates in NF-κB activation and that its deficiency leads to decreased IκB turnover in humans, highlighting an important regulatory component of this pathway.

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Section: Figuresupporting

confidence: 72%

Section: Figurementioning

confidence: 83%

Section: Figurementioning

confidence: 99%

“…All other plasmids used were described previously (1,3,16,25,28,(46)(47)(48). See Supplemental Table 1 for target sequences of the siRNA duplexes used.…”

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

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CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling

Starokadomskyy¹,

Gluck²,

Li³

et al. 2013

J. Clin. Invest.

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100

135

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Gene expression in the twilight of death

Pozhitkov

Noble

2017

BioEssays

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After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the "twilight of death" - the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the zebrafish and mouse reaching the conclusion that apparently thousands of transcripts significantly increase in abundance from life to several hours/days postmortem relative to live controls. Transcript dynamics of different genes provided "proof-of-principle" that models accurately predict an individual's elapsed-time-of-death (i.e. postmortem interval). While many transcripts were associated with survival and stress compensation, others were associated with epigenetic factors, developmental control, and cancer. Future studies are needed to determine whether the high incidence of cancer in transplant recipients is due to the postmortem processes in donor organs.

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COMMD1: A Multifunctional Regulatory Protein

Riera‐Romo¹

2017

J of Cellular Biochemistry

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The COMMD Protein Family is highly conserved among multicellular eukaryotic organisms and many orthologs of human COMMD genes have been found in different species of plants, invertebrates, lower vertebrates, and mammals. COMMD1 is the best characterized member of the family and is conserved among vertebrates. This protein represents a pleiotropic factor involved in the regulation of many cellular and physiological processes that include copper and cholesterol homeostasis, ionic transport, oxidative stress, protein aggregation, protein trafficking, NF-kB-mediated transcription, hypoxia induced transcription, DNA damage response, and oncogenesis. The present work reviews the molecular mechanisms and biological processes regulated by COMMD1 that have been described so far, emphasizing in the regulatory role of the protein and its importance for cellular homeostasis. J. Cell. Biochem. 119: 34-51, 2018. © 2017 KEY WORDS: COMMD1; COPPER METABOLISM; PROTEIN TRAFFICKING; IONIC TRANSPORT; TRANSCRIPTION REGULATION; ONCOGENESIS P rotein-Protein interactions (PPI) are crucial for the majority of biological processes, including macromolecular assemblies, enzymatic complexes, mitogenic events, signal transduction, metabolism, and regulation pathways [Li et al., 2004;Lev et al., 2013]. The identification of binding partners for particular proteins and the establishment of protein-protein networks are critical to comprehend many cellular and physiological functions [Moreira et al., 2007]. These studies are also important for drug design and discovery of novel molecular targets, with biological and clinical significance in the treatment of diverse pathologies [Cukuroglu et al., 2014].The COMMD (Copper Metabolism MURR1 Domain-containing) Protein Family, highly conserved in eukaryotic multicellular organisms, is implicated in the regulation of many biological processes through PPI [Bartuzi et al., 2013]. The specific functions of COMMD proteins are not defined, but they have been connected to the regulation of transcription factors like NF-kB [Ganesh et al., 2003;Burstein et al., 2005;de Bie et al., 2006]. Besides, some of these proteins are strongly suppressed in tumor cells, a finding that suggests antitumor activity [reviewed in Burstein et al., 2005]. COMMD1 is the best characterized member of the family and several partners have been known to interact with this protein [Vonk et al., 2010]. COMMD1 is implicated in many different cellular functions, such as copper balance, cholesterol homeostasis, ionic transport, transcription regulation, and oxidative stress [Vonk et al., 2010;Mao et al., 2011;Bartuzi et al., 2016]. Thus, it represents a pleiotropic factor essential for cellular homeostasis and a molecular target for modulation/disruption of pathological events. The current review describes the molecular mechanisms and biological processes regulated by COMMD1 that have been reported to date, emphasizing in the regulatory role of the protein and its implication in cellular homeostasis. COMMD PROTEIN FAMILY EVOLUTIONARY...

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COMMD1 (Copper Metabolism MURR1 Domain-containing Protein 1) Regulates Cullin RING Ligases by Preventing CAND1 (Cullin-associated Nedd8-dissociated Protein 1) Binding

Cited by 41 publications

References 40 publications

CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling

CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling

Gene expression in the twilight of death

COMMD1: A Multifunctional Regulatory Protein

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