Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBWG1M0)

• DOT Name: Cyclin-D1-binding protein 1 (CCNDBP1)
• Synonyms: Grap2 and cyclin-D-interacting protein; Human homolog of Maid
• Gene Name: CCNDBP1
• Related Disease:
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Hepatocellular carcinoma
  Hypercalcaemia
  Neoplasm
  Retinoblastoma
  Trichohepatoenteric syndrome
  Ulcerative colitis
  Wiskott-Aldrich syndrome
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: CCDB1_HUMAN
• PDB ID: 3AY5
• Pfam ID: PF20936 ; PF13324
• Sequence:
  MASATAPAAAVPTLASPLEQLRHLAEELRLLLPRVRVGEAQETTEEFNREMFWRRLNEAA
  VTVSREATTLTIVFSQLPLPSPQETQKFCEQVHAAIKAFIAVYYLLPKDQGITLRKLVRG
  ATLDIVDGMAQLMEVLSVTPTQSPENNDLISYNSVWVACQQMPQIPRDNKAAALLMLTKN
  VDFVKDAHEEMEQAVEECDPYSGLLNDTEENNSDNHNHEDDVLGFPSNQDLYWSEDDQEL
  IIPCLALVRASKACLKKIRMLVAENGKKDQVAQLDDIVDISDEISPSVDDLALSIYPPMC
  HLTVRINSAKLVSVLKKALEITKASHVTPQPEDSWIPLLINAIDHCMNRIKELTQSELEL
• Function: May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription.
• Tissue Specificity: Ubiquitously expressed. Expression is down-regulated in a variety of tumor types including breast, colon, prostate and rectal tumors, and is up-regulated in certain hepatic carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[5]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[6]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[7]
Wiskott-Aldrich syndrome	DISATMDB	Strong	Biomarker	[8]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[4]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[4]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[18]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Cyclin-D1-binding protein 1 (CCNDBP1).	[19]

References

• [1] GCIP/CCNDBP1, a helix-loop-helix protein, suppresses tumorigenesis.J Cell Biochem. 2007 Apr 15;100(6):1376-86. doi: 10.1002/jcb.21140.
• [2] Human homologue of maid is a useful marker protein in hepatocarcinogenesis.Gastroenterology. 2005 May;128(5):1369-80. doi: 10.1053/j.gastro.2005.03.014.
• [3] A tumor-secreted protein associated with human hypercalcemia of malignancy. Biology and molecular biology.Ann N Y Acad Sci. 1988;548:137-45. doi: 10.1111/j.1749-6632.1988.tb18800.x.
• [4] miR-9 Modulates Osteosarcoma Cell Growth by Targeting the GCIP Tumor Suppressor.Asian Pac J Cancer Prev. 2015;16(11):4509-13. doi: 10.7314/apjcp.2015.16.11.4509.
• [5] A novel senescence-evasion mechanism involving Grap2 and Cyclin D interacting protein inactivation by Ras associated with diabetes in cancer cells under doxorubicin treatment.Cancer Res. 2010 Jun 1;70(11):4357-65. doi: 10.1158/0008-5472.CAN-09-3791. Epub 2010 May 11.
• [6] Clinical review 16: Parathyroid hormone-related proteins: coming of age in the 1990s.J Clin Endocrinol Metab. 1990 Dec;71(6):1410-4. doi: 10.1210/jcem-71-6-1410.
• [7] miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.Inflamm Bowel Dis. 2015 Sep;21(9):2039-51. doi: 10.1097/MIB.0000000000000453.
• [8] Single-Turnover Activation of Arp2/3 Complex by Dip1 May Balance Nucleation of Linear versus Branched Actin Filaments.Curr Biol. 2019 Oct 7;29(19):3331-3338.e7. doi: 10.1016/j.cub.2019.08.023. Epub 2019 Sep 26.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [19] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.