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Review
. 2022 Oct 3:12:1009948.
doi: 10.3389/fonc.2022.1009948. eCollection 2022.

Multifunctions of CRIF1 in cancers and mitochondrial dysfunction

Yangzhou Jiang  1 , Yang Xiang  1 , Chuanchuan Lin  1 , Weiwei Zhang  1 , Zhenxing Yang  1 , Lixin Xiang  1 , Yanni Xiao  1 , Li Chen  1 , Qian Ran  1 , Zhongjun Li  1   2
Affiliations
Review

Multifunctions of CRIF1 in cancers and mitochondrial dysfunction

Yangzhou Jiang et al. Front Oncol. .

Erratum in

Abstract

Sustaining proliferative signaling and enabling replicative immortality are two important hallmarks of cancer. The complex of cyclin-dependent kinase (CDK) and its cyclin plays a decisive role in the transformation of the cell cycle and is also critical in the initiation and progression of cancer. CRIF1, a multifunctional factor, plays a pivotal role in a series of cell biological progresses such as cell cycle, cell proliferation, and energy metabolism. CRIF1 is best known as a negative regulator of the cell cycle, on account of directly binding to Gadd45 family proteins or CDK2. In addition, CRIF1 acts as a regulator of several transcription factors such as Nur77 and STAT3 and partly determines the proliferation of cancer cells. Many studies showed that the expression of CRIF1 is significantly altered in cancers and potentially regarded as a tumor suppressor. This suggests that _targeting CRIF1 would enhance the selectivity and sensitivity of cancer treatment. Moreover, CRIF1 might be an indispensable part of mitoribosome and is involved in the regulation of OXPHOS capacity. Further, CRIF1 is thought to be a novel _target for the underlying mechanism of diseases with mitochondrial dysfunctions. In summary, this review would conclude the latest aspects of studies about CRIF1 in cancers and mitochondria-related diseases, shed new light on _targeted therapy, and provide a more comprehensive holistic view.

Keywords: CR6-interacting factor 1; cancer treatment; cell cycle regulation; cell proliferation regulation; mitochondrial dysfunction; mitochondrial ribosomal protein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
CRIF1 regulates cell cycle, cell proliferation, and OXPHOS capacity. It could be a cancer therapeutic _target, and knocking down CRIF1 is an effective way to establish mitochondrial dysfunction in mice. CRIF1 binds to CDK2 and inhibits its activity ①. CRIF1 binds to Gadd45 family proteins and enhances its activity ②. CRIF1 increases P53 expression by coactivating with SNF5 ③. CRIF1 decreases STAT3 phosphorylation and inhibits cell proliferation ④. CRIF1 transports into the mitochondrial matrix, associates with the LSU of the mitoribosome, and regulates OXPHOS capacity ⑤.
Figure 2
Figure 2
In different types of cells, CRIF1 deficiency induces mitochondrial dysfunction and eventually causes different diseases. In vascular endothelial cells, mitochondrial dysfunction induced by CRIF1 deficiency potentially causes atherosclerosis. In brain cells, mitochondrial dysfunction induced by CRIF1 deficiency potentially causes Alzheimer’s diseases. In adipocytes, mitochondrial dysfunction induced by CRIF1 deficiency potentially causes diabetes mellitus type 2. In keratinocytes, mitochondrial dysfunction induced by CRIF1 deficiency potentially causes asthma.
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