The Emerging Picture of CDK11: Genetic, Functional and Medicinal Aspects

Paparidis, Nikolas Ferreira dos Santos; Canduri, Fernanda

doi:10.2174/0929867324666170815102036

Cited by 22 publications

(10 citation statements)

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“…CDK11 is a member of the serine/threonine protein kinase family. CDK11 plays a crucial role in cell proliferation and growth of cancers, such as breast cancer, ovarian cancer, multiple myeloma, and sarcoma [7–12]. Knockdown of CDK11 by shRNA or siRNA inhibits cancer cell growth and induces apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation

et al. 2019

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Background Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. Methods In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFβ) were further accessed in osteosarcoma. Results We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFβ expression in osteosarcoma cells. The CBFβ promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFβ is a direct transcriptional target of CDK11. High expression of CBFβ is associated with poor outcome in osteosarcoma patients. Expression of CBFβ contributes to the proliferation and metastatic behavior of osteosarcoma cells. Conclusions These data establish CBFβ as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFβ pathway may be a promising therapeutic strategy for osteosarcoma treatment. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation

et al. 2019

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“…It is encoded by two genes (CDC2L1 and CDC2L2) and produces three different isoforms, each with its own independent functions [6]. CDK11p46 exhibits a pro-apoptotic role, CDK11p58 functions during mitosis, promoting centrosome maturation and mitotic spindle assembly, and CDK11p110 regulates transcription and RNA splicing [143]. Overexpression and heightened activity of CDK11 has been noted in several cancers including breast, multiple myeloma, colon, and cervical cancer [6].…”

Section: Transcriptional and "Other" Cdksmentioning

confidence: 99%

CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Kohlmeyer

Gordon

Tanas

et al. 2020

IJMS

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Sarcomas represent one of the most challenging tumor types to treat due to their diverse nature and our incomplete understanding of their underlying biology. Recent work suggests cyclin-dependent kinase (CDK) pathway activation is a powerful driver of sarcomagenesis. CDK proteins participate in numerous cellular processes required for normal cell function, but their dysregulation is a hallmark of many pathologies including cancer. The contributions and significance of aberrant CDK activity to sarcoma development, however, is only partly understood. Here, we describe what is known about CDK-related alterations in the most common subtypes of sarcoma and highlight areas that warrant further investigation. As disruptions in CDK pathways appear in most, if not all, subtypes of sarcoma, we discuss the history and value of pharmacologically targeting CDKs to combat these tumors. The goals of this review are to (1) assess the prevalence and importance of CDK pathway alterations in sarcomas, (2) highlight the gap in knowledge for certain CDKs in these tumors, and (3) provide insight into studies focused on CDK inhibition for sarcoma treatment. Overall, growing evidence demonstrates a crucial role for activated CDKs in sarcoma development and as important targets for sarcoma therapy.

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“…The larger 110 kDa protein isoform, CDK11 p110 , is mainly associated with RNA splicing and generates the CDK11 p58 isoform during the G 2 –M phase of the cell cycle. A 58 kDa isoform, CDK11 p58 , is mitosis‐specific and a 46 kDa isoform, CDK11 p46 , is apoptosis‐specific . Similar to other members of the CDK family, CDK11 takes part in both cell cycle control and RNA transcription regulation.…”

Section: Biology and Regulation Of Cdks In Hccmentioning

confidence: 99%

“…A 58 kDa isoform, CDK11 p58 , is mitosis-specific and a 46 kDa isoform, CDK11 p46 , is apoptosis-specific. 90,91 Similar to other members of the CDK family, CDK11 takes part in both cell cycle control and RNA transcription regulation. Cyclin-dependent kinase 11 associates with cyclin L, directly binding to various splicing factors and playing a critical role in pre-mRNA splicing.…”

Section: Cyclin-dependent Kinase 11mentioning

confidence: 99%

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

Shen

Dean²,

et al. 2019

Hepatology Research

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Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.

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The Emerging Picture of CDK11: Genetic, Functional and Medicinal Aspects

Cited by 22 publications

References 0 publications

Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation

Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation

CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

Role of cyclin‐dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway

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