Molecule Information

General Information of the Molecule (ID: Mol01909)

• Name: Retinoblastoma-like protein 1 (RBL1) ,Homo sapiens
• Synonyms: RBL1
• Molecule Type: Protein
• Gene Name: RBL1
• Gene ID: 5933
• Location: chr20:36,996,349-37,095,997[-]
• Sequence:
  MFEDKPHAEGAAVVAAAGEALQALCQELNLDEGSAAEALDDFTAIRGNYSLEGEVTHWLA
  CSLYVACRKSIIPTVGKGIMEGNCVSLTRILRSAKLSLIQFFSKMKKWMDMSNLPQEFRE
  RIERLERNFEVSTVIFKKYEPIFLDIFQNPYEEPPKLPRSRKQRRIPCSVKDLFNFCWTL
  FVYTKGNFRMIGDDLVNSYHLLLCCLDLIFANAIMCPNRQDLLNPSFKGLPSDFHTADFT
  ASEEPPCIIAVLCELHDGLLVEAKGIKEHYFKPYISKLFDRKILKGECLLDLSSFTDNSK
  AVNKEYEEYVLTVGDFDERIFLGADAEEEIGTPRKFTRDTPLGKLTAQANVEYNLQQHFE
  KKRSFAPSTPLTGRRYLREKEAVITPVASATQSVSRLQSIVAGLKNAPSDQLINIFESCV
  RNPVENIMKILKGIGETFCQHYTQSTDEQPGSHIDFAVNRLKLAEILYYKILETVMVQET
  RRLHGMDMSVLLEQDIFHRSLMACCLEIVLFAYSSPRTFPWIIEVLNLQPFYFYKVIEVV
  IRSEEGLSRDMVKHLNSIEEQILESLAWSHDSALWEALQVSANKVPTCEEVIFPNNFETG
  NGGNVQGHLPLMPMSPLMHPRVKEVRTDSGSLRRDMQPLSPISVHERYSSPTAGSAKRRL
  FGEDPPKEMLMDKIITEGTKLKIAPSSSITAENVSILPGQTLLTMATAPVTGTTGHKVTI
  PLHGVANDAGEITLIPLSMNTNQESKVKSPVSLTAHSLIGASPKQTNLTKAQEVHSTGIN
  RPKRTGSLALFYRKVYHLASVRLRDLCLKLDVSNELRRKIWTCFEFTLVHCPDLMKDRHL
  DQLLLCAFYIMAKVTKEERTFQEIMKSYRNQPQANSHVYRSVLLKSIPREVVAYNKNIND
  DFEMIDCDLEDATKTPDCSSGPVKEERGDLIKFYNTIYVGRVKSFALKYDLANQDHMMDA
  PPLSPFPHIKQQPGSPRRISQQHSIYISPHKNGSGLTPRSALLYKFNGSPSKSLKDINNM
  IRQGEQRTKKRVIAIDSDAESPAKRVCQENDDVLLKRLQDVVSERANH
• Function: Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation. May act as a tumor suppressor.
• Uniprot ID: RBL1_HUMAN
• Ensembl ID: ENSG00000080839

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

LY2835219

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: LY2835219
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: LY2835219
• Molecule Alteration: Missense mutation; p.A193T
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Palbociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Palbociclib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Palbociclib
• Molecule Alteration: Missense mutation; p.A193T
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Ribociclib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Ribociclib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Ribociclib
• Molecule Alteration: Missense mutation; p.A193T
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: The tumor suppressor RB is the aforementioned key checkpoint in the cell cycle. As the primary target of CDK4/6 inhibitors, RB was considered to be one of the most important biomarkers of sensitivity to therapy. In this scenario, loss of RB is the evident cause of resistance to CDK4/6 inhibitors, and various preclinical studies have supported this hypothesis. In addition, some preclinical and clinical studies have also reported that mutations in RB are responsible for the resistance. A study using glioblastoma xenograft cells, a missense mutation in exon 2 of RB(A193T) resulted in resistance to CDK4/6 inhibitors.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.03E-53; Fold-change: 1.58E-01; Z-score: 8.91E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.02E-14; Fold-change: 9.11E-02; Z-score: 6.65E-01

References

• Ref 1: Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review .Int J Cancer. 2019 Sep 1;145(5):1179-1188. doi: 10.1002/ijc.32020. Epub 2019 Jan 7. 10.1002/ijc.32020